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Sample records for experimental hyperdynamic sepsis

  1. Hyperdynamic sepsis modifies a PEEP-mediated redistribution in organ blood flows

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    Bersten, A.D.; Gnidec, A.A.; Rutledge, F.S.; Sibbald, W.J. (Univ. of Western Ontario, London (Canada))

    1990-05-01

    Changes in organ blood flow (Q) produced by 20 cm H2O positive end-expiratory pressure (PEEP) were measured before and after the induction of hyperdynamic sepsis in nine unanesthetized sheep. During the baseline nonseptic study, PEEP was associated with a 9% fall in thermodilution-measured systemic Q, although arterial perfusing pressures were unaffected. Concurrently, microsphere-derived Q was maintained to the brain and heart, but fell to liver, spleen, pancreas, kidney, large intestine, and gastrocnemius. Twenty-four to 36 h after cecal ligation and perforation, a pre-PEEP septic study demonstrated an increase in all of the cardiac index (CI) and systemic O2 delivery when compared with the nonseptic study, whereas whole-body O2 extraction was depressed. Although PEEP depressed systemic Q during the septic study to a greater extent than during the nonseptic study (p less than 0.02), absolute organ Q fell only to pancreas, liver, and spleen. Relative to the simultaneous fall in the CI, Q to some splanchnic organs was not depressed by PEEP to the same magnitude in the septic as in the nonseptic study. When an infusion of Ringer's lactate subsequently restored systemic Q to pre-PEEP septic levels, individual flows that had been depressed by PEEP were not restored. Furthermore, Q-kidney continued to fall, such that the postfluid Q-kidney (-19%) was significantly less than was demonstrated in the pre-PEEP septic study. We postulate that differences noted in the distribution of organ Q between the nonseptic and hyperdynamic septic studies after the application of PEEP were secondary to the vasculopathy of sepsis and/or an alteration in the function of specific organ microcirculations. However, these data do not address whether the changes in organ Q distribution after a PEEP-mediated depression in systemic Q during sepsis significantly restricted tissue DO2.

  2. An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism.

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    Byrne, Liam; Obonyo, Nchafatso G; Diab, Sara; Dunster, Kimble; Passmore, Margaret; Boon, Ai Ching; Hoe, Louise See; Hay, Karen; Van Haren, Frank; Tung, John-Paul; Cullen, Louise; Shekar, Kiran; Maitland, Kathryn; Fraser, John F

    2017-05-17

    Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock. This difference may exaggerate the importance of hypoperfusion as a causative factor in organ dysfunction. This study sought to develop an ovine model of hyperdynamic endotoxemia and assess if there is evidence of impaired oxidative metabolism in the vital organs. Eight sheep had microdialysis catheters implanted into the brain, heart, liver, kidney and arterial circulation. Shock was induced with a 4hr escalating dose infusion of endotoxin. After 3hrs vasopressor support was initiated with noradrenaline and vasopressin. Animals were monitored for 12hrs after endotoxemia. Blood samples were recovered for haemoglobin, white blood cell count, creatinine and proinflammatory cytokines (IL-1Beta, IL-6 & IL-8). The endotoxin infusion was successful in producing distributive shock with the mean arterial pressure decreasing from 84.5 ± 12.8 mmHg to 49 ± 8.03 mmHg (p shock. There was evidence of impaired oxidative metabolism in the liver suggesting impaired splanchnic perfusion. This may be a modifiable factor in the progression to multiple organ dysfunction and death.

  3. Hyperdynamics for entropic systems

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    Zhou, Xin; Jiang, Yi; Kremer, Kurt

    2006-01-01

    We develop a generalized hyperdynamics method, which is able to simulate slow dynamics in atomistic general (both energy and entropy-dominated) systems. We show that a few functionals of the pair correlation function, involving two-body entropy, form a low-dimensional collective space, which...... is a good approximation that is able to distinguish stable and transitional conformations. A bias potential, which raises the energy in stable regions, is constructed on the fly. We examine the slowly nucleation processes of a Lennard-Jones gas and show that our new method can generate correct long time...

  4. [Establishment and evaluation of experimental sepsis mouse model].

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    Wang, Li-Yan; Xu, Ruo-Nan; Han, Gen-Cheng; Wang, Ren-Xi; Chen, Guo-Jiang; Xiao, He; Hou, Chun-Mei; Shen, Bei-Fen; Li, Yan

    2010-06-01

    After treating with chemotherapy or immunosuppressant, malignant diseases of hematopoietic system such as leukemia, malignant lymphoma and aplastic anemia usually induced severe infection such as sepsis. Sepsis which is hard to be diagnosed causes high death rate. This study was purposed to establish an experimental sepsis mouse model so as to provide a basis for pathogenesis and intervention study. A classic caecal ligation and puncture (CLP) was used to establish experimental sepsis model. ELISA was used to detect levels of C5a, IL-6, TNFalpha, and IFN-gamma. Flow Cytometry was applied to measure apoptosis of lymphocytes in thymus and mesentery. The pathologic changes of thymus and spleen were confirmed by HE staining. The results showed that almost 70%-80% mice died at 72 hours after CLP. Only approximate 20% animal survived during finite time, mice in CLP group had significant weight lose. Meanwhile large release of different inflammatory mediators which are related with sepsis (C5a, IL-6, TNF-alpha, and IFN-gamma) was observed after CLP. Apoptosis of lymphocytes in thymus and mesentery lymphonodus was enhanced markedly after CLP. Significantly pathologic injury was also observed in thymus and spleen. It is concluded that a mouse model of experimental sepsis was successfully established by caecal ligation and puncture which can well mimic the clinical symptom of sepsis. The experimental sepsis mouse model provides an excellent tool for exploring the pathogenesis and intervention ways for sepsis accompanied with complicated malignant hematological diseases in vivo.

  5. Experimental treatments for mitochondrial dysfunction in sepsis: A narrative review

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    Guilang Zheng

    2015-01-01

    Full Text Available Sepsis is a systemic inflammatory response to infection. Sepsis, which can lead to severe sepsis, septic shock, and multiple organ dysfunction syndrome, is an important cause of mortality. Pathogenesis is extremely complex. In recent years, cell hypoxia caused by mitochondrial dysfunction has become a hot research field. Sepsis damages the structure and function of mitochondria, conversely, mitochondrial dysfunction aggravated sepsis. The treatment of sepsis lacks effective specific drugs. The aim of this paper is to undertake a narrative review of the current experimental treatment for mitochondrial dysfunction in sepsis. The search was conducted in PubMed databases and Web of Science databases from 1950 to January 2014. A total of 1,090 references were retrieved by the search, of which 121 researches met all the inclusion criteria were included. Articles on the relationship between sepsis and mitochondria, and drugs used for mitochondrial dysfunction in sepsis were reviewed retrospectively. The drugs were divided into four categories: (1 Drug related to mitochondrial matrix and respiratory chain, (2 drugs of mitochondrial antioxidant and free radical scavengers, (3 drugs related to mitochondrial membrane stability, (4 hormone therapy for septic mitochondria. In animal experiments, many drugs show good results. However, clinical research lacks. In future studies, the urgent need is to develop promising drugs in clinical trials.

  6. 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.

  7. Immunomodulatory role of leptin treatment in experimental sepsis caused by gram negative bacteria

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    KOCA, Cemile; KAVAKLI, Havva ŞAHİN; ALICI, Özlem

    2011-01-01

    To investigate the effect of leptin treatment on circulating inflammatory cytokines and on tissue damage in experimental rat model of gram-negative sepsis. Materials and methods: Adult male Wistar rats, 28 in total, were randomly divided into 4 groups (n = 7): sham, leptin, sepsis, and sepsis group treated with leptin (sepsis+leptin). Sepsis was induced by intraperitoneal (ip) injection of 2 × 1010 CFU of Escherichia coli ATCC 25922. Leptin and sepsis+leptin groups received a single dose ip ...

  8. Experimental meningococcal sepsis in congenic transgenic mice expressing human transferrin.

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    Marek Szatanik

    Full Text Available Severe meningococcal sepsis is still of high morbidity and mortality. Its management may be improved by an experimental model allowing better understanding of its pathophysiology. We developed an animal model of meningococcal sepsis in transgenic BALB/c mice expressing human transferrin. We studied experimental meningococcal sepsis in congenic transgenic BALB/c mice expressing human transferrin by transcriptional profiling using microarray analysis of blood and brain samples. Genes encoding acute phase proteins, chemokines and cytokines constituted the largest strongly regulated groups. Dynamic bioluminescence imaging further showed high blood bacterial loads that were further enhanced after a primary viral infection by influenza A virus. Moreover, IL-1 receptor-associated kinase-3 (IRAK-3 was induced in infected mice. IRAK-3 is a negative regulator of Toll-dependant signaling and its induction may impair innate immunity and hence result in an immunocompromised state allowing bacterial survival and systemic spread during sepsis. This new approach should enable detailed analysis of the pathophysiology of meningococcal sepsis and its relationships with flu infection.

  9. Sepsis

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

    2016-01-01

    , 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...

  10. Sepsis

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    Perner, Anders; Rhodes, Andrew; Venkatesh, Bala

    2017-01-01

    . Thus, further improvements in supportive interventions and organisation of care are likely to have a substantial impact upon global health. In this narrative review, invited experts describe the challenges and progress to be made in sepsis research and care in the near future. We focus on supportive...

  11. A Systematic Review of Rhubarb (a Traditional Chinese Medicine) Used for the Treatment of Experimental Sepsis.

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    Lai, Fang; Zhang, Yan; Xie, Dong-Ping; Mai, Shu-Tao; Weng, Yan-Na; Du, Jiong-Dong; Wu, Guang-Ping; Zheng, Jing-Xia; Han, Yun

    2015-01-01

    Sepsis is a global major health problem in great need for more effective therapy. For thousands of years, Rhubarb had been used for various diseases including severe infection. Pharmacological studies and trials reported that Rhubarb may be effective in treating sepsis, but the efficacy and the quality of evidence remain unclear since there is no systematic review on Rhubarb for sepsis. The present study is the first systematic review of Rhubarb used for the treatment of experimental sepsis in both English and Chinese literatures by identifying 27 studies from 7 databases. It showed that Rhubarb might be effective in reducing injuries in gastrointestinal tract, lung, and liver induced by sepsis, and its potential mechanisms might include reducing oxidative stress and inflammation, ameliorating microcirculatory disturbance, and maintaining immune balance. Yet the positive findings should be interpreted with caution due to poor methodological quality. In a word, Rhubarb might be a promising candidate that is worth further clinical and experimental trials for sepsis therapy.

  12. Brain infection following experimental Staphylococcus aureus sepsis in pigs

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    Astrup, Lærke Boye; Iburg, Tine Moesgaard; Nielsen, Ole Lerberg

    2010-01-01

    Introduction: Sepsis is a major problem in humans and both the incidence and mortality is increasing. Multiple microabcesses can be found in the brain of septic patients. Staphylococcus aureus is one of the most common causes of sepsis and brain abscesses. S. aureus is also a frequent cause...... pigs were kept as controls. The pigs were euthanized in groups of four at either 6, 12, 24 or 48 h post infection. The brain was collected from all the animals and examined histologically. Results: All the inoculated pigs developed sepsis and 7 out of 12 animals had microabscesses in the prosencephalon...

  13. The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis

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    Møller, Søren; Bendtsen, Flemming

    2017-01-01

    transplantation and point to the pathophysiological significance of portal hypertension. In this paper we aimed to review current knowledge on the pathophysiology of arterial vasodilatation and the hyperdynamic circulation in cirrhosis. This article is protected by copyright. All rights reserved....

  14. Determinants of the hyperdynamic circulation and central hypovolaemia in cirrhosis

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    Møller, Søren; Hobolth, Lise; Winkler, Christine

    2011-01-01

    Patients with advanced cirrhosis often develop a hyperdynamic circulation with central hypovolaemia. The events that initiate the systemic haemodynamic abnormalities and the coupling of these factors to splanchnic haemodynamics are still unclear. Objective On the basis of a large population...

  15. Hyperdynamics boost factor achievable with an ideal bias potential

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    Huang, Chen; Perez, Danny; Voter, Arthur F.

    2015-08-01

    Hyperdynamics is a powerful method to significantly extend the time scales amenable to molecular dynamics simulation of infrequent events. One outstanding challenge, however, is the development of the so-called bias potential required by the method. In this work, we design a bias potential using information about all minimum energy pathways (MEPs) out of the current state. While this approach is not suitable for use in an actual hyperdynamics simulation, because the pathways are generally not known in advance, it allows us to show that it is possible to come very close to the theoretical boost limit of hyperdynamics while maintaining high accuracy. We demonstrate this by applying this MEP-based hyperdynamics (MEP-HD) to metallic surface diffusion systems. In most cases, MEP-HD gives boost factors that are orders of magnitude larger than the best existing bias potential, indicating that further development of hyperdynamics bias potentials could have a significant payoff. Finally, we discuss potential practical uses of MEP-HD, including the possibility of developing MEP-HD into a true hyperdynamics.

  16. Combination of dehydroepiandrosterone and orthovanadate administration reduces intestinal leukocyte recruitment in models of experimental sepsis.

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    Al-Banna, Nadia; Pavlovic, Dragan; Sharawi, Nivin; Bac, Vo Hoai; Jaskulski, Mathis; Balzer, Claudius; Weber, Stefan; Nedeljkov, Vladimir; Lehmann, Christian

    2014-09-01

    Dehydroepiandrosterone (DHEA) was shown to improve the immune function and survival in experimental sepsis. This study examined the effect of DHEA on intestinal leukocyte recruitment during experimental sepsis, considering factors of gender (male, female and ovariectomized female animals) and combined treatment using orthovanadate (OV) in two models of sepsis. Male rats underwent colon ascendens stent peritonitis (CASP) or endotoxemia. DHEA was administered after induction of experimental sepsis. Changes in leukocyte adherence and capillary perfusion (measured as intestinal functional capillary density - FCD) were assessed using intravital microscopy. While DHEA increased baseline leukocyte adherence in control animals, DHEA reduced leukocyte adherence and increased FCD in male animals with CASP. These effects were also observed in DHEA-treated ovariectomized female rats with CASP. Similarly, the administration of DHEA reduced the number of adherent leukocytes to intestinal venules by 30% in the endotoxemia model. The combined treatment of DHEA and OV significantly reduced adherence of leukocytes to intestinal venules and improved FCD. Our results indicate that DHEA is able to reduce intestinal leukocyte recruitment induced by experimental sepsis. Combination of DHEA with OV inhibits leukocyte adherence to intestinal endothelium, similar to what is achieved by the single administration of DHEA but with significantly improved FCD. These findings suggest a potential role for DHEA and OV in clinical sepsis. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Experimental Cannabinoid 2 Receptor-Mediated Immune Modulation in Sepsis

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    J. Sardinha

    2014-01-01

    Full Text Available Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics. The present study explored the effect of modulating the CB2 receptor pathway in an acute sepsis mouse model. Endotoxemia was induced by intravenous injection of lipopolysaccharide (LPS in mice and intestinal microcirculation was assessed through intravital microscopy. We found that HU308 (CB2 receptor agonist reduced the number of adherent leukocytes in submucosal venules but did not restore muscular and mucosal villi FCD in endotoxemic mice. AM630 (CB2 receptor antagonist maintained the level of adherent leukocytes induced by LPS but further reduced muscular and mucosal villi FCD. URB597 (FAAH inhibitor and JZL184 (MAGL inhibitor both reduced the number of adherent leukocytes in submucosal venules but did not restore the mucosal villi FCD. Using various compounds we have shown different mechanisms of activating CB2 receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis.

  18. Cannabinoid Receptor 2 Protects against Acute Experimental Sepsis in Mice

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    Huan Gui

    2013-01-01

    Full Text Available The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock. Despite significant advances in the understanding of the molecular and cellular mechanisms of septic shock, it is still one of the most frequent and serious problems confronting clinicians in the treatments. And the effects of cannabinoid receptor 2 (CB2R on the sepsis still remain undefined. The present study was aimed to explore the role and mechanism of CB2R in acute sepsis model of mice. Here, we found that mice were more vulnerable for lipopolysaccharide- (LPS- induced death and inflammation after CB2R deletion (CB2R−/−. CB2R agonist, GW405833, could significantly extend the survival rate and decrease serum proinflammatory cytokines in LPS-treated mice. GW405833 dose-dependently inhibits proinflammatory cytokines release in splenocytes and peritoneal macrophages as well as splenocytes proliferation, and these effects were partly abolished in CB2R−/− splenocytes but completely abolished in CB2R−/− peritoneal macrophages. Further studies showed that GW405833 inhibits LPS-induced phosphorylation of ERK1/2 and STAT3 and blocks IκBα degradation and NF-κB p65 nuclear translocation in macrophages. All data together showed that CB2R provides a protection and is a potential therapeutic target for the sepsis.

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

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    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M

    2016-01-01

    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......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......(-1) ; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh-cuff deflation failed to induce...

  20. Heart rate variability in porcine progressive peritonitis-induced sepsis

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    Dagmar eJarkovska

    2016-01-01

    Full Text Available Accumulating evidence suggests that heart rate variability (HRV alterations could serve as an indicator of sepsis progression and outcome, however, the relationships of HRV and major pathophysiological processes of sepsis remain unclear. Therefore, in this experimental study HRV was investigated in a clinically relevant long-term porcine model of severe sepsis/septic shock. HRV was analyzed by several methods and the parameters were correlated with pathophysiological processes of sepsis.In 16 anesthetized, mechanically ventilated and instrumented domestic pigs of either gender, sepsis was induced by fecal peritonitis. Experimental subjects were screened up to the refractory shock development or death. ECG was continuously recorded throughout the experiment, afterwards RR intervals were detected and HRV parameters computed automatically using custom made measurement and analysis MATLAB routines. In all septic animals, progressive hyperdynamic septic shock developed. The statistical measures of HRV, geometrical measures of HRV and Poincaré plot analysis revealed a pronounced reduction of HRV that developed quickly upon the onset of sepsis and was maintained throughout the experiment. The frequency domain analysis demonstrated a decrease in the high frequency component and increase in the low frequency component together with an increase of the low/high frequency component ratio. The reduction of HRV parameters preceded sepsis-associated hemodynamic changes including heart rate increase or shock progression.In a clinically relevant porcine model of peritonitis-induced progressive septic shock, reduction of HRV parameters heralded sepsis development. HRV reduction was associated with a pronounced parasympathetic inhibition and a shift of sympathovagal balance. Early reduction of HRV may serve as a non-invasive and sensitive marker of systemic inflammatory syndrome, thereby widening the therapeutic window for early interventions.

  1. IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

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    Kenneth Lyn-Kew

    2010-06-01

    Full Text Available Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM recovered from the lungs of mice undergoing cecal ligation and puncture (CLP display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3 and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/- mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.

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

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    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

  3. Immunomodulatory intervention in sepsis by multidrug-resistant Pseudomonas aeruginosa with thalidomide: an experimental study

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    Perrea Despina

    2005-06-01

    Full Text Available Abstract Background Thalidomide is an inhibitor of tumour necrosis factor-alpha (TNFα that has been proven effective for the treatment of experimental sepsis by Escherichia coli. It was tested whether it might behave as an effective immunomodulator in experimental sepsis by multidrug-resistant (MDR Pseudomonas aeruginosa. Methods Sepsis was induced by the intraperitoneal injection of 1 × 108 cfu/kg inoculum of the test isolate in a total of 109 Wistar rats divided in three groups as follows: group A controls; group B administered seed oil 30 minutes before bacterial challenge; and group C administered 50 mg/kg of thalidomide diluted in seed oil 30 minutes before bacterial challenge. Blood was sampled for estimation of endotoxins (LPS, TNFα, interferon-gamma (IFNγ, nitric oxide (NO and malondialdehyde (MDA. LPS was measured by the QCL-1000 LAL assay, TNFα and IFNγ by ELISA, NO by a colorimetric assay and MDA by the thiobarbiturate assay. Results Mean (± SE survival of groups A, B and C were 18.60 ± 1.84, 12.60 ± 0.60 and 30.50 ± 6.62 hours (p of comparisons A to C equal to 0.043 and B to C equal to 0.002. Decreased TNFα and NO levels were found in sera of animals of group C compared to group A. Plasma levels of LPS, MDA and IFNγ did not differ between groups. Conclusion Intake of thalidomide considerably prolonged survival in experimental sepsis by MDR P.aeruginosa an effect probably attributed to decrease of serum TNFα.

  4. Effect of Induced Mild Hypothermia on Acid-Base Balance During Experimental Acute Sepsis in Rats.

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    Léon, Karelle; Pichavant-Rafini, Karine; Ollivier, Hélène; L'Her, Erwan

    2015-09-01

    The aim of this study was to determine the effect of induced mild hypothermia (34°C) on acid-base balance in septic rats. Twenty-eight male Sprague-Dawley rats median weight 306 g, range 251-333 g were used. After anesthesia and when the target temperature was reached (normothermia: 38°C or induced mild hypothermia: 34°C), sepsis was induced by cecal ligation and perforation. Measurements of cardiopulmonary parameters and blood samples were performed at T0h (occurring immediately after chirurgical procedures), T2h, T4h (at each temperature), and T6h (at 34°C only). Blood oxygen saturation, heart and respiratory rates, arterial blood pH, carbon dioxide partial pressure, sodium, potassium, chloride and calcium concentrations, hematocrit, blood lactate, tumor necrosis factor-α and interleukin-6 concentrations were measured on anesthetized rats. Other parameters such as bicarbonate concentration, hemoglobin concentration, base excess, and anion gap were estimated from measured parameters. Main results showed that an increase in both cytokines concentrations was observed in septic rats compared with sham rats. This increase was less marked at 34°C compared with 38°C. Moreover, sepsis induction led to a marked metabolic acidosis and hypothermia delayed this acidosis. Induced mild hypothermia delays the evolution of cytokines and metabolic acidosis during experimental sepsis.

  5. A novel natural compound from garlic (Allium sativum L.) with therapeutic effects against experimental polymicrobial sepsis.

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    Lee, Sung Kyun; Park, Yoo Jung; Ko, Min Jung; Wang, Ziyu; Lee, Ha Young; Choi, Young Whan; Bae, Yoe-Sik

    2015-08-28

    Sepsis is a serious, life-threatening, infectious disease. In this study, we demonstrate that sucrose methyl 3-formyl-4-methylpentanoate (SMFM), a novel natural compound isolated from garlic (Allium sativum L.), markedly enhances survival rates by inhibiting lung inflammation in a cecal ligation and puncture (CLP) experimental polymicrobial sepsis model. SMFM strongly reduced bacterial colony units from peritoneal fluid in CLP mice by stimulating the generation of reactive oxygen species. Lymphocyte apoptosis in spleens from CLP mice was also markedly decreased by SMFM administration. SMFM also significantly inhibited the production of proinflammatory cytokines, such as TNF-α, interleukin-1β (IL-1β) and IL-6, in CLP mice. Lipopolysaccharide-stimulated production of TNF-α and IL-6 were also strongly inhibited by SMFM in mouse bone marrow-derived macrophages. Taken together, our results indicate that SMFM has therapeutic effects against polymicrobial sepsis that are mediated by enhanced microbial killing and blockage of cytokine storm. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis.

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    Colbert, James F; Ford, Joshay A; Haeger, Sarah M; Yang, Yimu; Dailey, Kyrie L; Allison, Kristen C; Neudecker, Viola; Evans, Christopher M; Richardson, Vanessa L; Brodsky, Kelley S; Faubel, Sarah; Eltzschig, Holger K; Schmidt, Eric P; Ginde, Adit A

    2017-08-01

    Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability. Copyright © 2017 the American Physiological Society.

  7. In vitro and in vivo effects of subinhibitory concentrations of clindamycin on experimental Klebsiella pneumoniae sepsis.

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    Arbo, A; Mancilla, J; Alpuche, C; Santos, J I

    1990-01-01

    We studied the effect of subinhibitory doses of clindamycin on the course of experimental Klebsiella pneumoniae sepsis. Wistar rats were injected intraperitoneally with an inoculum containing 5 x 10(6) colony-forming units of K. pneumoniae resistant to clindamycin (minimum inhibitory concentration greater than 128 micrograms/ml) and then distributed to receive clindamycin 10 mg/kg/day or placebo for 10 days. All animals were bacteremic at 3 h. When the magnitude of bacteremia was compared, no difference was seen during the first 24 h; however, by 72 h the clindamycin-treated group had a significant decrease in the number of colony-forming units per milliliter blood (p less than 0.01). The mortality rate showed a tendency to decrease in the treated group (0%) as compared with the control group (30%). By 120 h, 3 of the 9 (33%) surviving animals from the control group were still bacteremic versus 0 of 11 (0%) in the clindamycin-treated group. These results suggest that subinhibitory clindamycin therapy can improve bacterial clearance and survival during the course of experimental K. pneumoniae sepsis.

  8. Similar Microcirculatory Alterations in Patients with Normodynamic and Hyperdynamic Septic Shock

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    Edul, Vanina S. Kanoore; Ince, Can; Vazquez, Alejandro Risso; Rubatto, Paolo N.; Espinoza, Emilio D. Valenzuela; Welsh, Sebastián; Enrico, Carolina; Dubin, Arnaldo

    2016-01-01

    Rationale: In normodynamic septic shock, the quantitative assessment of sublingual microcirculation has shown decreases in perfused vascular density and red blood cell velocity. However, no studies have been performed in hyperdynamic septic shock. Objectives: To characterize the microcirculatory

  9. Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis

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    L. Rahal

    Full Text Available Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min and enalaprilat infusion (0.02 mg kg-1 min-1 for 60 min in randomized groups. The following groups were studied: controls (fluid infusion, N = 4, E1 (enalaprilat infusion followed by fluid infusion, N = 5 and E2 (fluid infusion followed by enalaprilat infusion, N = 5. All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO, portal vein blood flow (PVBF, systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.

  10. Detrimental effect of apoptosis of lymphocytes at an early time point of experimental abdominal sepsis

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    Atmatzidis Stefanos

    2011-11-01

    Full Text Available Abstract Background Apoptosis of lymphocytes is considered a late sequelum in the sepsis cascade. The role of apoptosis of lymphocytes as a driver of final outcome was investigated. Methods Abdominal sepsis was induced after cecal ligation and puncture (CLP in 31 rabbits. Blood was sampled at serial time intervals and peripheral blood mononuclear cells (PBMCs were isolated. Apoptosis of lymphocytes and monocytes was measured through flow cytometric analysis. PBMCs were stimulated with LPS and Pam3Cys for the release of tumor necrosis factor-alpha (TNFα. Tissue bacterial growth was quantitatively measured. In a second set of experiments, CLP was performed in another 40 rabbits; 20 received single intravenous infusions of ciprofloxacin and of metronidazole 4 hours after surgery. Results Animals were divided into two groups based on the percentage of lymphocyte apoptosis at 4 hours after surgery; less than or equal to 32% and more than 32%. Survival of the former was shorter than the latter (p: 0.017. Tissue growth was similar between groups. Apoptosis of lymphocytes and of monocytes was lower in the former group over follow-up. Release of ΤNFα did not differ. The above findings on survival were repeated in the second set of experiments. Administration of antimicrobials prolonged survival of the former group (p: 0.039 but not of the latter group (pNS. Conclusions Lymphocyte apoptosis at an early time point of experimental peritonitis is a major driver for death. A lower percentage of apoptosis leads earlier to death. Antimicrobials were beneficial even at that disease state.

  11. Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis

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    L. Rahal

    2006-09-01

    Full Text Available Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min and enalaprilat infusion (0.02 mg kg-1 min-1 for 60 min in randomized groups. The following groups were studied: controls (fluid infusion, N = 4, E1 (enalaprilat infusion followed by fluid infusion, N = 5 and E2 (fluid infusion followed by enalaprilat infusion, N = 5. All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO, portal vein blood flow (PVBF, systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.

  12. The primate circadian timekeeping system in a hyperdynamic environment

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    Fuller, C. A.

    1984-01-01

    The effect of hyperdynamic field (12 d at 1.5 G and 35 d at 2.0 G phases, preceded and followed by 1.0 G phases of 15 and 18 days, respectively) on the circadian rhythm in the feeding and drinking of the squirrel monkey was studied. Two lighting regimens were employed: (1) the 24-hr light-dark cycle (LD 12:12) at all G phases and (2) constant light (LL) during the two 1.0 G phases and a 2.0 G phase. In the LD regimen, both feeding and drinking rhythms were entrained with the 24-hr periods at all G levels, but a phase delay occurred in high G environment. In the LL regimen, the rhythm persisted with a free-running period greater than 24 hours and an increase at 2.0 G, compared to the 1.0 G phases. Thus, although the circadian rhythm is functional at high G, some of its components appear to be regulated at different homeostatic levels.

  13. Alteration of Lysophosphatidylcholine-Related Metabolic Parameters in the Plasma of Mice with Experimental Sepsis.

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    Ahn, Won-Gyun; Jung, Jun-Sub; Kwon, Hyeok Yil; Song, Dong-Keun

    2017-04-01

    Plasma concentration of lysophosphatidylcholine (LPC) was reported to decrease in patients with sepsis. However, the mechanisms of sepsis-induced decrease in plasma LPC levels are not currently well known. In mice subjected to cecal ligation and puncture (CLP), a model of polymicrobial peritoneal sepsis, we examined alterations in LPC-related metabolic parameters in plasma, i.e., the plasma concentration of LPC-related substances (i.e., phosphatidylcholine (PC) and lysophosphatidic acid (LPA)), and activities or levels in the plasma of some enzymes that can be involved in the regulation of plasma LPC concentration (i.e., secretory phospholipase A2 (sPLA2), lecithin:cholesterol acyltransferase (LCAT), acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT), and autotaxin (ATX)), as well as plasma albumin concentration. We found that levels of LPC and albumin and enzyme activities of LCAT, ATX, and sPLA2 were decreased, whereas levels of PC, LPA, and LPCAT1-3 were increased in the plasma of mice subjected to CLP. Bacterial peritonitis led to alterations in all the measured LPC-related metabolic parameters in the plasma, which could potentially contribute to sepsis-induced decrease in plasma LPC levels. These findings could lead to the novel biomarkers of sepsis.

  14. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

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    Castro, C.L. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Aguiar-Nemer, A.S. [Departamento de Nutrição, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG (Brazil); Castro-Faria-Neto, H.C. [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ (Brazil); Barros, F.R. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Rocha, E.M.S. [Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Silva-Fonseca, V.A. [Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2013-12-10

    The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

  15. Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat

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    Valentina Selmi

    2016-11-01

    Full Text Available Abstract Background Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB with consequent albuminuria. We examined whether the pharmacokinetics–pharmacodynamics (PK/PD of ceftriaxone (CTX, an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. Methods A prospective, experimental, randomized study was carried out in adult male Sprague–Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP. Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC. The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90% for 80 and 100% of Tfree > minimum inhibitory concentration (MIC for 80 and 100% of dosing interval. Measurements and main results After CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104–1 × 105 CFU in CLP rats. CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004, while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p  90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee. Conclusions Sepsis causes changes in

  16. Cationic liposomes containing antioxidants reduces pulmonary injury in experimental model of sepsis: Liposomes antioxidants reduces pulmonary damage.

    Science.gov (United States)

    Galvão, Andre Martins; Galvão, Júlia Siqueira; Pereira, Marcela Araújo; Cadena, Pabyton Gonçalves; Magalhães, Nereide Stella Santos; Fink, James B; de Andrade, Armele Dornelas; Castro, Celia Maria Machado Barbosa de; de Sousa Maia, Maria Bernadete

    2016-09-01

    The intracellular redox state of alveolar cells is a determining factor for tolerance to oxidative and pro-inflammatory stresses. This study investigated the effects of intratracheal co-administration of antioxidants encapsulated in liposomes on the lungs of rats subjected to sepsis. For this, male rats subjected to sepsis induced by lipopolysaccharide from Escherichia coli or placebo operation were treated (intratracheally) with antibiotic, 0.9% saline and antioxidants encapsulated or non-encapsulated in liposomes. Experimental model of sepsis by cecal ligation and puncture (CLP) was performed in order to expose the cecum. The cecum was then gently squeezed to extrude a small amount of feces from the perforation site. As an index of oxidative damage, superoxide anions, lipid peroxidation, protein carbonyls, catalase activity, nitrates/nitrites, cell viability and mortality rate were measured. Infected animals treated with antibiotic plus antioxidants encapsulated in liposomes showed reduced levels of superoxide anion (54% or 7.650±1.263 nmol/min/mg protein), lipid peroxidation (33% or 0.117±0.041 nmol/mg protein), protein carbonyl (57% or 0.039 ± 0.022 nmol/mg protein) and mortality rate (3.3%), p value antioxidants should be explored as coadjuvants in the treatment of pulmonary oxidative damage. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. An NMR metabolomics investigation of perturbations after treatment with Chinese herbal medicine formula in an experimental model of sepsis.

    Science.gov (United States)

    Li, Yunzhi; Liu, Hongbin; Wu, Xianzhong; Li, Donghua; Huang, Jing

    2013-05-01

    Sepsis is a leading cause of morbidity and mortality in critically ill patients. OMICS and systems pharmacology approaches offer the promise of new therapeutic candidates for the treatment of patients with sepsis. Qin-Re-Jie-Du (QRJD) and Liang-Xue-Huo-Xue (LXHX) are two traditional Chinese herbal medicine (CHM) formulas with putative effects in sepsis treatment. The present study aimed to assess their efficacy in an experimental model of sepsis in rats (cecal ligation and punctures) and investigate their mechanism of action using a 1H-NMR metabolomics approach. Rats were randomly divided into four groups (i.e., model group, sham control group, and two CHM treatment groups). Water extracts of QRJD and LXHX were orally administered to the two CHM treatment groups at a dose of 24 g/kg of body weight, once daily for 3 consecutive days. The same volume of 0.9% saline solution was orally administered to the model and sham surgery groups. Plasma samples were collected and measured using 600 MHz 1H-NMR spectroscopy. As a result, 18 potential metabolite biomarkers involved in multiple metabolic pathways, including increased energy metabolism, fat mobilization, and disrupted amino acid metabolism, were identified in septic rats. The principal component analysis (PCA) and partial least squares discriminant (PLS-DA) plots of the metabolic state correlated well with the mortality and clinical biochemistry results. An analysis of potential biomarkers verified the holistic effects of the two CHM formulas. The Cori cycle was positively regulated in the QRJD-treated formulas treatment group but also inhibited in the LXHX-treated group, which demonstrates the different efficacies of these solutions in septic rats.

  18. The German Quality Network Sepsis: study protocol for the evaluation of a quality collaborative on decreasing sepsis-related mortality in a quasi-experimental difference-in-differences design.

    Science.gov (United States)

    Schwarzkopf, Daniel; Rüddel, Hendrik; Gründling, Matthias; Putensen, Christian; Reinhart, Konrad

    2018-01-18

    While sepsis-related mortality decreased substantially in other developed countries, mortality of severe sepsis remained as high as 44% in Germany. A recent German cluster randomized trial was not able to improve guideline adherence and decrease sepsis-related mortality within the participating hospitals, partly based on lacking support by hospital management and lacking resources for documentation of prospective data. Thus, more pragmatic approaches are needed to improve quality of sepsis care in Germany. The primary objective of the study is to decrease sepsis-related hospital mortality within a quality collaborative relying on claims data. The German Quality Network Sepsis (GQNS) is a quality collaborative involving 75 hospitals. This study protocol describes the conduction and evaluation of the start-up period of the GQNS running from March 2016 to August 2018. Democratic structures assure participatory action, a study coordination bureau provides central support and resources, and local interdisciplinary quality improvement teams implement changes within the participating hospitals. Quarterly quality reports focusing on risk-adjusted hospital mortality in cases with sepsis based on claims data are provided. Hospitals committed to publish their individual risk-adjusted mortality compared to the German average. A complex risk-model is used to control for differences in patient-related risk factors. Hospitals are encouraged to implement a bundle of interventions, e.g., interdisciplinary case analyses, external peer-reviews, hospital-wide staff education, and implementation of rapid response teams. The effectiveness of the GQNS is evaluated in a quasi-experimental difference-in-differences design by comparing the change of hospital mortality of cases with sepsis with organ dysfunction from a retrospective baseline period (January 2014 to December 2015) and the intervention period (April 2016 to March 2018) between the participating hospitals and all other German

  19. Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis.

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    DongYu Liang

    Full Text Available Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3, a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP-induced sepsis in mice.C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation.Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05. Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis.Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis.

  20. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis

    Science.gov (United States)

    Schmidt, Eric P; Yang, Yimu; Janssen, William J; Gandjeva, Aneta; Perez, Mario J; Barthel, Lea; Zemans, Rachel L; Bowman, Joel C; Koyanagi, Dan E; Yunt, Zulma X; Smith, Lynelle P; Cheng, Sara S; Overdier, Katherine H; Thompson, Kathy R; Geraci, Mark W; Douglas, Ivor S; Pearse, David B; Tuder, Rubin M

    2013-01-01

    Sepsis, a systemic inflammatory response to infection, commonly progresses to acute lung injury (ALI), an inflammatory lung disease with high morbidity. We postulated that sepsis-associated ALI is initiated by degradation of the pulmonary endothelial glycocalyx, leading to neutrophil adherence and inflammation. Using intravital microscopy, we found that endotoxemia in mice rapidly induced pulmonary microvascular glycocalyx degradation via tumor necrosis factor-α (TNF-α)-dependent mechanisms. Glycocalyx degradation involved the specific loss of heparan sulfate and coincided with activation of endothelial heparanase, a TNF-α–responsive, heparan sulfate–specific glucuronidase. Glycocalyx degradation increased the availability of endothelial surface adhesion molecules to circulating microspheres and contributed to neutrophil adhesion. Heparanase inhibition prevented endotoxemia-associated glycocalyx loss and neutrophil adhesion and, accordingly, attenuated sepsis-induced ALI and mortality in mice. These findings are potentially relevant to human disease, as sepsis-associated respiratory failure in humans was associated with higher plasma heparan sulfate degradation activity; moreover, heparanase content was higher in human lung biopsies showing diffuse alveolar damage than in normal human lung tissue. PMID:22820644

  1. Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients.

    Science.gov (United States)

    Ruiz, Carolina; Hernandez, Glenn; Godoy, Cristian; Downey, Patricio; Andresen, Max; Bruhn, Alejandro

    2010-01-01

    Previous studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients. This was a prospective, non-randomized study at a 16-bed, medical-surgical intensive care unit of a university hospital. We included 12 severe hyperdynamic septic shock patients (norepinephrine requirements > 0.3 μg/kg/min and cardiac index > 3.0 L/min/m2) who underwent a 12-hour HVHF as a rescue therapy according to a predefined algorithm. Sublingual microcirculation (Microscan for NTSC, Microvision Medical), systemic hemodynamics and perfusion parameters were assessed at baseline, at 12 hours of HVHF, and 6 hours after stopping HVHF. Microcirculatory flow index increased after 12 hours of HVHF and this increase persisted 6 hours after stopping HVHF. A similar trend was observed for the proportion of perfused microvessels. The increase in microcirculatory blood flow was inversely correlated with baseline levels. There was no significant change in microvascular density or heterogeneity during or after HVHF. Mean arterial pressure and systemic vascular resistance increased while lactate levels decreased after the 12-hour HVHF. The use of HVHF as a rescue therapy in patients with severe hyperdynamic septic shock does not deteriorate sublingual microcirculatory blood flow despite the increase in systemic vascular resistance.

  2. Experimental acute lung injury induces multi-organ epigenetic modifications in key angiogenic genes implicated in sepsis-associated endothelial dysfunction.

    Science.gov (United States)

    Bomsztyk, Karol; Mar, Daniel; An, Dowon; Sharifian, Roya; Mikula, Michal; Gharib, Sina A; Altemeier, William A; Liles, W Conrad; Denisenko, Oleg

    2015-05-11

    The Tie2/angiopoietin (Tie2/Ang) and vascular endothelial growth factor receptor-ligand systems (VEGFR/VEGF) are recognized to play important roles in the regulation of microvascular endothelial function. Downregulation of these genes during sepsis has been implicated in the pathogenesis of sepsis-related microvascular leak and multiple organ dysfunction syndrome. Mechanisms responsible for dysregulation of angiogenic genes in sepsis are poorly defined. Western blot, reverse transcription-polymerase chain reaction, and multiplex chromatin immunoprecipitation platform (Matrix ChIP) were used to investigate serum albumin leak, changes in gene expression, and associated epigenetic alterations in a murine model of acute lung injury-induced sepsis (ALI-sepsis). Experimental ALI-sepsis induced microvascular leak and downregulation of expression of Angpt1 (Ang1), Tek (Tie2), and Kdr (Vegfr2 or Flk-1) genes in the lung, kidney, and liver. These changes correlate with a decrease in RNA polymerase II density at these genes, and the greatest response was observed in the lung. ALI-sepsis reduced levels of transcription-permissive histone H3 lysine acetylation (H3KAc) at these loci in all examined tissues. Decreases in permissive H3K4m3 and H3Km2 marks were detected only in the lung. In contrast, only minimal alterations in transcription-repressive histone modifications (H3K27m3, H3K9m2, H3K9m3, and H4K20m3) were observed in all tissues. Our results demonstrate that decreases in transcription-permissive, but not increases in transcription-repressive, histone modifications at Angpt1, Tek, and Kdr are a systemic, rather than a lung-restricted, response, involving key end-organs in experimental ALI-sepsis. Given that ventilator-associated pneumonia is a major cause of sepsis in critically ill patients, elucidation of mechanisms mediating epigenetic alterations during sepsis provides fundamental new insights into the pathogenesis of sepsis-induced microvascular leak and subsequent

  3. Expression of Toll-like receptors (TLRs in the lungs of an experimental sepsis mouse model.

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    Anargyros Bakopoulos

    Full Text Available Sepsis is a condition characterized by high mortality rates and often accompanied by multiple-organ dysfunction. During sepsis, respiratory system may be affected and possibly result in acute respiratory distress syndrome (ARDS. Toll-like receptors (TLRs, as a first line defense against invading pathogens, seem to be highly expressed in septic states. Therefore, expression of TLRs in the lungs of a sepsis animal model could indicate the involvement of the respiratory system and appear as a severity index of the clinical course.A total of 72 C57BL/6J mice, aged 12-14 weeks, were studied. The animals were divided into 3 sepsis (S groups (24h, 48h and 72h and 3 control (C groups (24h, 48h and 72h, each consisting of 12 mice. The S-groups were subjected to cecal ligation and puncture (CLP while the C-groups had a sham operation performed. Blood samples were drawn from all groups. Total blood count analysis was performed along with the measurement of certain biochemical markers. Additionally, lung tissues were harvested and the expression of TLRs, namely TLR 2, TLR 3, TLR 4 and TLR 7 were evaluated by means of immunofluorescence (IF and qRT-PCR (quantitative-Polymerase Chain Reaction. Statistical analysis was performed by using one-way ANOVA followed by student t-test. Results were considered statistically significant when p<0.05.WBCs and lymphocytes were decreased in all S-groups compared to the corresponding C-groups (p<0.05, while RBCs showed a gradual decline in S-groups with the lowest levels appearing in the S72 group. Only, monocytes were higher in S-groups, especially between S48-C48 (p<0.05 and S72-C72 (p<0.05. Creatinine, IL-10 and IL-6 levels were significantly increased in the S-groups compared to the corresponding C-groups (S24 vs C24, S48 vs C48 and S72 vs C72, p<0.05. IF showed that expression of TLRs 2, 3, 4 and 7 was increased in all S-groups compared to the time-adjusted C-groups (p<0.05. Similarly, qRT-PCR revealed that expression

  4. Exercise training prevents skeletal muscle damage in an experimental sepsis model

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    Carla Werlang Coelho

    2013-01-01

    Full Text Available OBJECTIVE: Oxidative stress plays an important role in skeletal muscle damage in sepsis. Aerobic exercise can decrease oxidative stress and enhance antioxidant defenses. Therefore, it was hypothesized that aerobic exercise training before a sepsis stimulus could attenuate skeletal muscle damage by modulating oxidative stress. Thus, the aim of this study was to evaluate the effects of aerobic physical preconditioning on the different mechanisms that are involved in sepsis-induced myopathy. METHODS: Male Wistar rats were randomly assigned to either the untrained or trained group. The exercise training protocol consisted of an eight-week treadmill program. After the training protocol, the animals from both groups were randomly assigned to either a sham group or a cecal ligation and perforation surgery group. Thus, the groups were as follows: sham, cecal ligation and perforation, sham trained, and cecal ligation and perforation trained. Five days after surgery, the animals were euthanized and their soleus and plantaris muscles were harvested. Fiber cross-sectional area, creatine kinase, thiobarbituric acid reactive species, carbonyl, catalase and superoxide dismutase activities were measured. RESULTS: The fiber cross-sectional area was smaller, and the creatine kinase, thiobarbituric acid reactive species and carbonyl levels were higher in both muscles in the cecal ligation and perforation group than in the sham and cecal ligation and perforation trained groups. The muscle superoxide dismutase activity was higher in the cecal ligation and perforation trained group than in the sham and cecal ligation and perforation groups. The muscle catalase activity was lower in the cecal ligation and perforation group than in the sham group. CONCLUSION: In summary, aerobic physical preconditioning prevents atrophy, lipid peroxidation and protein oxidation and improves superoxide dismutase activity in the skeletal muscles of septic rats.

  5. Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis

    Science.gov (United States)

    2013-01-01

    Introduction Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. Methods Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. Results Seven days following CLP, propranolol improved survival versus control (P propranolol-treated rats were approximately 23% lower than control rats (P propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. Conclusions These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection. PMID:24020447

  6. New sepsis biomarkers

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    Dolores Limongi

    2016-06-01

    Full Text Available Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes. Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity, specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis, timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  7. Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis.

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    Sperber, Jesper; Lipcsey, Miklós; Larsson, Anders; Larsson, Anders; Sjölin, Jan; Castegren, Markus

    2015-05-10

    Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome. 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels. TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb. Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia

  8. Severe hyponatraemia during sepsis and marijuana addiction

    National Research Council Canada - National Science Library

    Catalano, Concetta; Seck, Sidy; Enia, Giuseppe

    2011-01-01

    .... He was a long-term user of marijuana. The association between severe recurrent hyponatraemia during sepsis and marijuana addiction might not be casual, since experimental data show that vasopressin release induced by sepsis is modulated...

  9. Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis: a prospective study.

    Science.gov (United States)

    Ostrowski, Sisse R; Berg, Ronan M G; Windeløv, Nis A; Meyer, Martin A S; Plovsing, Ronni R; Møller, Kirsten; Johansson, Pär I

    2013-10-01

    The aim of this study was to investigate associations between circulating catecholamines, endothelial damage, and coagulopathy in experimental human endotoxemia and septic patients. Nine healthy male volunteers undergoing endotoxemia (4-hour 0.5 ng/kg/hour infusion of E. coli lipopolysaccharide, blood sampling at 0, 4, and 6 hours) and 20 patients with severe sepsis. Analysis of plasma biomarkers (adrenaline, noradrenaline, thrombomodulin, syndecan-1, soluble vascular endothelial cadherin, histone-complexed DNA fragments, soluble CD40 ligand [sCD40L], protein C, tissue-type plasminogen activator, plasminogen activator inhibitor 1) and routine coagulation tests. Endotoxemia increased heart rate, temperature, white blood cell count, C-reactive protein and procalcitonin, decreased blood pressure and induced a hemostatic response with platelet consumption, reduced protein C and sCD40L levels and enhanced tissue-type plasminogen activator release (all Pdisease severity scores (noradrenaline and thrombomodulin) (all Pmarkers of hypocoagulability and disease severity. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Frontline Science: HMGB1 induces neutrophil dysfunction in experimental sepsis and in patients who survive septic shock.

    Science.gov (United States)

    Grégoire, Murielle; Tadié, Jean-Marc; Uhel, Fabrice; Gacouin, Arnaud; Piau, Caroline; Bone, Nathaniel; Le Tulzo, Yves; Abraham, Edward; Tarte, Karin; Zmijewski, Jaroslaw W

    2017-06-01

    Sepsis is accompanied by the initial activation of proinflammatory pathways and long-lasting immunosuppression that appears to contribute to late-occurring mortality. Although high-mobility group box 1 (HMGB1) is involved in many aspects of inflammation, its role in sepsis-induced immune suppression remains unclear. In this study, we examined HMGB1's contribution to neutrophil NADPH oxidase activity dysfunction and associated neutrophil-dependent bacterial clearance in mice subjected to sepsis and in patients who survive septic shock. Using a murine model of polymicrobial septic peritonitis, we demonstrated that treatment with anti-HMGB1 Ab significantly diminished sepsis-induced dysfunction of neutrophil NADPH oxidase activity. In a subsequent set of experiments, we found that blocking HMGB1 preserved the ability of neutrophils from patients recovering from septic shock to activate NADPH oxidase. Taken together, our data suggest that HMGB1 accumulation in the late phase of sepsis plays a specific role in the development of postsepsis immunosuppression and specifically affects neutrophil-dependent antibacterial defense mechanisms. Thus, blocking HMGB1 may be a promising therapeutic intervention to diminish the adverse effects of sepsis-induced immunosuppression. © Society for Leukocyte Biology.

  11. Abdominal sepsis

    NARCIS (Netherlands)

    Boldingh, Quirine J. J.; de Vries, Fleur E. E.; Boermeester, Marja A.

    2017-01-01

    Purpose of review To summarize the recent evidence on the treatment of abdominal sepsis with a specific emphasis on the surgical treatment. Recent findings A multitude of surgical approaches towards abdominal sepsis are practised. Recent evidence shows that immediate closure of the abdomen has a

  12. Brain perfusion in sepsis.

    Science.gov (United States)

    Taccone, Fabio Silvio; Scolletta, Sabino; Franchi, Federico; Donadello, Katia; Oddo, Mauro

    2013-03-01

    Brain dysfunction is a frequent complication of sepsis, usually defined as "sepsis-associated encephalopathy" (SAE). Its pathophysiology is complex and related to numerous processes and pathways, while the exact mechanisms producing neurological impairment in septic patients remain incompletely elucidated. Alterations of the cerebral blood flow (CBF) may represent a key component for the development of SAE. Reduction of CBF may be caused by cerebral vasoconstriction, either induced by inflammation or hypocapnia. Endothelial dysfunction associated with sepsis leads to impairment of microcirculation and cerebral metabolic uncoupling that may further reduce brain perfusion so that CBF becomes inadequate to satisfy brain cellular needs. The natural autoregulatory mechanisms that protect the brain from reduced/ inadequate CBF can be impaired in septic patients, especially in those with shock or delirium, and this further contributes to cerebral ischemia if blood pressure drops below critical thresholds. Sedative agents alter cerebro-vascular reactivity and may significantly reduce CBF. Although disorders of brain perfusion and alteration of CBF and cerebral autoregulation are frequently observed in humans with sepsis, their exact role in the pathogenesis of SAE remains unknown. Brain perfusion can further become inadequate due to cerebral microcirculatory dysfunction, as evidenced in the experimental setting. Microvascular alterations can be implicated in the development of electrophysiological abnormalities observed during sepsis and contribute to neurological alterations in septic animals. The aim of this review is to provide an update on the pathophysiology of brain perfusion in sepsis, with a particular focus on human clinical investigation and novel tools for CBF monitoring in septic patients.

  13. Vitamin D and sepsis

    Directory of Open Access Journals (Sweden)

    Morteza Hariri Ahari

    2014-09-01

    Full Text Available Vitamin D receptors are located in body tissues and cells.  In various physiological processes of the body the primary circulating form of vitamin D, 25-hydroxyvitamin D, will become the active form, 1,25-dihydroxyvitamin D, through many enzymatic. Although different functions of vitamin D has been identified, reducing the possibility of several chronic diseases, including common cancers, autoimmune, infectious, and cardiovascular diseases is proposed as the major role of this component. According to various experimental and clinical studies, vitamin D affects the immune system activity. In this review we study the possible effects of vitamin D on sepsis. The purpose of this review is to evaluate and summarize the role of vitamin D in the immune system, with particular focus on infections and sepsis. We studied different areas related to vitamin D in the literature review including its roles sepsis and infection incidence, as well as seasonal and racial variation in sepsis. Based on evidence, vitamin D positively affects the immune system, so it might act as a therapeutic strategy. Despite several experimental studies which demonstrated the beneficial effects of vitamin D on improved functioning of the immune system, its association with prevention or management of infections and sepsis is not revealed through clinical investigations.

  14. Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients.

    Science.gov (United States)

    Evans, David C; Khoo, Kendrick M; Radulescu, Andrei; Cook, Charles H; Gerlach, Anthony T; Papadimos, Thomas J; Steinberg, Steven M; Stawicki, Stanislaw Pa; Eiferman, Daniel S

    2014-10-01

    Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB), beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%). Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB) patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB) when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response.

  15. Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients

    Directory of Open Access Journals (Sweden)

    David C Evans

    2014-01-01

    Full Text Available Purpose: Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. Materials and Methods: Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB, beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. Results: Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%. Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. Conclusions: Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response.

  16. Streptococcal Sepsis

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. Sepsis Fact Sheet

    Science.gov (United States)

    ... Education About NIGMS NIGMS Home > Science Education > Sepsis Sepsis Tagline (Optional) Middle/Main Content Area PDF Version ( ... KB) En español Other Fact Sheets What is sepsis? Sepsis is a serious medical condition. It is ...

  19. Sepsis (For Parents)

    Science.gov (United States)

    ... Late for the Flu Vaccine? Eating Disorders Arrhythmias 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 ...

  20. Liver dysfunction and phosphatidylinositol-3-kinase signalling in early sepsis: experimental studies in rodent models of peritonitis.

    Directory of Open Access Journals (Sweden)

    Peter Recknagel

    Full Text Available Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests.In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3Kγ gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid [TDCA] observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59, these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87.Liver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is necessary to extend these

  1. Puerperal sepsis.

    Science.gov (United States)

    Arulkumaran, N; Singer, M

    2013-12-01

    Infections during pregnancy are relatively prevalent, and the majority of cases are managed well in the community. Occasionally, however, infections may be life-threatening. Sepsis may be associated with multiple organ dysfunction and a high mortality. The treatment of sepsis is time critical and requires early fluid resuscitation and antibiotics. Early involvement of other specialties and allied health-care professionals to provide a multidisciplinary approach to patient care is important. Continuous monitoring of maternal vital signs and provision of supportive care for multiple organ dysfunction are best done within the intensive care unit. Despite advances in patient care, the mortality rate associated with maternal sepsis remains high. Health-care services in low-income countries face particular problems that account for an increased incidence of puerperal sepsis and maternal mortality. These include lack of access to health care, septic abortions and a greater incidence of human immunodeficiency virus. The key to management of sepsis is early recognition, aggressive resuscitation, antibiotic administration and source control. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Coagulation abnormalities in sepsis.

    Science.gov (United States)

    Tsao, Cheng-Ming; Ho, Shung-Tai; Wu, Chin-Chen

    2015-03-01

    Although the pathophysiology of sepsis has been elucidated with the passage of time, sepsis may be regarded as an uncontrolled inflammatory and procoagulant response to infection. The hemostatic changes in sepsis range from subclinical activation of blood coagulation to acute disseminated intravascular coagulation (DIC). DIC is characterized by widespread microvascular thrombosis, which contributes to multiple organ dysfunction/failure, and subsequent consumption of platelets and coagulation factors, eventually causing bleeding manifestations. The diagnosis of DIC can be made using routinely available laboratory tests, scoring algorithms, and thromboelastography. In this cascade of events, the inhibition of coagulation activation and platelet function is conjectured as a useful tool for attenuating inflammatory response and improving outcomes in sepsis. A number of clinical trials of anticoagulants were performed, but none of them have been recognized as a standard therapy because recombinant activated protein C was withdrawn from the market owing to its insufficient efficacy in a randomized controlled trial. However, these subgroup analyses of activated protein C, antithrombin, and thrombomodulin trials show that overt coagulation activation is strongly associated with the best therapeutic effect of the inhibitor. In addition, antiplatelet drugs, including acetylsalicylic acid, P2Y12 inhibitors, and glycoprotein IIb/IIIa antagonists, may reduce organ failure and mortality in the experimental model of sepsis without a concomitant increased bleeding risk, which should be supported by solid clinical data. For a state-of-the-art treatment of sepsis, the efficacy of anticoagulant and antiplatelet agents needs to be proved in further large-scale prospective, interventional, randomized validation trials. Copyright © 2014. Published by Elsevier B.V.

  3. The evolutionary logic of sepsis.

    Science.gov (United States)

    Rózsa, Lajos; Apari, Péter; Sulyok, Mihály; Tappe, Dennis; Bodó, Imre; Hardi, Richárd; Müller, Viktor

    2017-11-01

    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

  4. Glial cell-derived neurotrophic factor alleviates sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nicotinic acetylcholine receptors in an experimental rat model of neuromyopathy.

    Science.gov (United States)

    Wang, Xin; Min, Su; Xie, Fei; Yang, Jun; Li, Liang; Chen, Jingyuan

    2018-02-05

    Sepsis-induced neuromuscular dysfunction results from up-regulation of the expression of γ- and α7-nicotinic acetylcholine receptors (nAChR). Although glial cell derived neurotrophic factor (GDNF) has been implicated in repairing and supporting neurons, little is known about the effects of GDNF on demyelination of nerves in sepsis. In this study, we tested the hypothesis that GDNF could alleviate sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nAChR in an experimental rat model of neuromyopathy. Rats were randomly divided into a sham group and a sepsis group. Levels of inflammatory factors, muscle function, and nicotinic acetylcholine receptors were tested in rats after cecal ligation and puncture (CLP). At 24 h after CLP, GDNF was injected around the sciatic nerve of sepsis rats, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining was used to detect the expression of nAChRs. GDNF and its downstream effector (Erk1/2 and GFR-α), neuregulin-1 (NRG-1) and γ- and α7-nAChR were measured using Western blot analysis. The expression of GDNF reached a minimum at 24 h after CLP. Compared with the sham group, the release of cytokines and the expression of γ- and α7-nAChR were significantly increased in the sepsis group. The administration of GDNF significantly alleviated sepsis-induced neuromuscular dysfunction, as well as reducing the expression of γ- and α7-nAChR. In addition, the expression of Erk1/2, GFR-α, NRG-1 were significantly increased after GDNF treatment. GDNF administration may improve patient outcomes by reducing the demyelination of nerves and the expression of γ- and α7-nAChR. Copyright © 2018. Published by Elsevier Inc.

  5. Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Berg, Ronan M G; Windeløv, Nis A

    2013-01-01

    The aim of this study was to investigate associations between circulating catecholamines, endothelial damage, and coagulopathy in experimental human endotoxemia and septic patients.......The aim of this study was to investigate associations between circulating catecholamines, endothelial damage, and coagulopathy in experimental human endotoxemia and septic patients....

  6. Neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Angelica Dessì

    2014-06-01

    Full Text Available In this paper on neonatal sepsis, after a short presentation of etiopathogenesis and physiopathology, we will briefly present the clinical picture, the diagnosis and the therapy. Concerning diagnosis, we will focus our attention on procalcitonin (PCT, serum amyloid A (SAA, presepsin (sCD14 and metabolomics. Three practical tables complete the review. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  7. Increase in seizure susceptibility in sepsis like condition explained by spiking cytokines and altered adhesion molecules level with impaired blood brain barrier integrity in experimental model of rats treated with lipopolysaccharides.

    Science.gov (United States)

    Sewal, Rakesh K; Modi, Manish; Saikia, Uma Nahar; Chakrabarti, Amitava; Medhi, Bikash

    2017-09-01

    Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Sepsis is a condition which initiates a cascade of a surge of inflammatory mediators. Interplay between seizures and inflammation other than of brain origin is yet to be explored. The present study was designed to evaluate the seizure susceptibility in experimental models of lipopolysaccharide (LPS) induced sepsis. Experimental sepsis was induced using lipopolysaccharides in Wistar rats. Valproic acid, dexametasone were given to two different groups of animals along with LPS. Two groups of animals were subjected to administration of vehicle and LPS respectively with no other treatment. 24h later, animals were subjected to seizures by using either maximal electro shock or pentylenetetrazole. Seizures related parameters, oxidative stress and TNF-α, IL-6, IL-1β, ICAM-1, ICAM-2, VCAM-1, MMP-9 level in serum and brain samples were evaluated. Histopathological and blood brain barrier permeability studies were conducted. Seizures were decreased in valproic acid treated animals. Reduced oxidative stress was seen in dexamethasone plus valproic acid treated groups as compared to LPS alone treated group. TNF-α, IL-6, IL-1β, ICAM-1, VCAM-1, MMP-9 levels were found increased in LPS treated animals whereas a reverse observation was noted for ICAM-2 level in brain and serum. Histopathological findings confirmed the successful establishment of sepsis like state in animals. Blood brain barrier permeability was found increased in LPS treated groups of animals. Seizure susceptibility may escalate during the sepsis like inflammatory conditions and curbing the inflammatory state might reverse the phenomenon. Copyright © 2017. Published by Elsevier B.V.

  8. Contribution of the platelet activating factor signaling pathway to cerebral microcirculatory dysfunction during experimental sepsis by ExoU producing Pseudomonas aeruginosa.

    Science.gov (United States)

    Plotkowski, Maria Cristina; Estato, Vanessa; Santos, Sabrina Alves; da Silva, Mauricio Costa Alves; Miranda, Aline Silva; de Miranda, Pedro Elias; Pinho, Vanessa; Tibiriça, Eduardo; Morandi, Verônica; Teixeira, Mauro Martins; Vianna, Albanita; Saliba, Alessandra Mattos

    2015-10-01

    Intravital microscopy was used to assess the involvement of ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, in dysfunction of cerebral microcirculation during experimental pneumosepsis. Cortical vessels from mice intratracheally infected with low density of the ExoU-producing PA103 P. aeruginosa strain exhibited increased leukocyte rolling and adhesion to venule endothelium, decreased capillar density and impaired arteriolar response to vasoactive acetylcholine. These phenomena were mediated by the platelet activating factor receptor (PAFR) pathway because they were reversed in mice treated with a PAFR antagonist prior to infection. Brains from PA103-infected animals exhibited a perivascular inflammatory infiltration that was not detected in animals infected with an exoU deficient mutant or in mice treated with the PAFR antagonist and infected with the wild type bacteria. No effect on brain capillary density was detected in mice infected with the PAO1 P. aeruginosa strain, which do not produce ExoU. Finally, after PA103 infection, mice with a targeted deletion of the PAFR gene exhibited higher brain capillary density and lower leukocyte adhesion to venule endothelium, as well as lower increase of systemic inflammatory cytokines, when compared to wild-type mice. Altogether, our results establish a role for PAFR in mediating ExoU-induced cerebral microvascular failure in a murine model of sepsis. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Homeostasis in Primates in the Hyperdynamic Environment. [circadian timekeeping and effects of lower body positive pressure on sleep

    Science.gov (United States)

    Fuller, C. A.

    1985-01-01

    The influence of chronic centrifugation upon the homestatic regulation of the circadian timekeeping system was examined. The interactions of body temperature regulation and the behavioral state of arousal were studied by evaluating the influence of cephalic fluid shifts induced by lower body positive air pressure (LBPP), upon these systems. The small diurnal squirrel monkey (Saimiri sciureus) was used as the non-human primate model. Results show that the circadian timekeeping system of these primates is functional in the hyperdynamic environment, however, some of its components appear to be regulated at different homeostatic levels. The LBPP resulted in an approximate 0.7 C decrease in DBT (p 0.01). However, although on video some animals appeared drowsy during LBPP, sleep recording revealed no significant changes in state of arousal. Thus, the physiological mechanisms underlying this lowering of body temperature can be independent of the arousal state.

  10. The impact of a hyperdynamic left ventricle on right ventricular function measurements in preterm infants with a patent ductus arteriosus.

    Science.gov (United States)

    Breatnach, Colm R; Franklin, Orla; James, Adam T; McCallion, Naomi; El-Khuffash, Afif

    2017-09-01

    Right ventricular (RV) functional assessment in premature infants includes basal longitudinal strain (RV BLS), RV systolic tissue Doppler velocity (RV s'), tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (FAC). A hyperdynamic left ventricle (LV) may influence RV measures of displacement (TAPSE) and velocity (RV s') but not measures of relative change of length (RV BLS) or area (FAC). We aimed to explore this hypothesis in preterm infants with a patent ductus arteriosus (PDA). We measured LV function (ejection fraction (LV EF); left ventricular output) and RV function (RV BLS; RV s'; TAPSE; FAC) on days 1, 2 and 5-7 in infants function measurements were compared between the groups using two-way analysis of variance with repeated measures. 121 infants with a mean (SD) gestation and birth weight of 26.8 (1.4) weeks and 968 (250) g were enrolled. By days 5-7, the PDA remained open in 83 (69%), with evidence of hyperdynamic LV function. There was no difference in RV s' (5.3 (0.9) vs 5.1 (1.0) cm/s, p=0.3) or TAPSE (6.2 (1.3) vs 6.1 (1.2) mm, p=0.7) between infants with and without a PDA, but infants in the PDA group had lower RV FAC (41 (8) vs 47 (10) %, pfunctional parameters must be taken into account when interpreting of RV function using those techniques. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. THE ENDOTHELIUM IN SEPSIS

    NARCIS (Netherlands)

    Ince, Can; Mayeux, Philip R.; Nguyen, Trung; Gomez, Hernando; Kellum, John A.; Ospina-Tascón, Gustavo A.; Hernandez, Glenn; Murray, Patrick; de Backer, Daniel

    2016-01-01

    Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other

  12. The endothelium in sepsis

    NARCIS (Netherlands)

    C. Ince (Can); P.R. Mayeux (Philip R.); T. Nguyen (Trung); H. Gomez (Hernando); J.A. Kellum (John A.); G.A. Ospina-Tascon (Gustavo A); G. Hernandez (Glenn); P. Murray (Patrick); D. de Backer (Daniel)

    2016-01-01

    textabstractSepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among

  13. Cardiorenal Syndromes and Sepsis

    Directory of Open Access Journals (Sweden)

    C. Chelazzi

    2011-01-01

    Full Text Available The cardiorenal syndrome is a clinical and pathophysiological entity defined as the concomitant presence of renal and cardiovascular dysfunction. In patients with severe sepsis and septic shock, acute cardiovascular, and renal derangements are common, that is, the septic cardiorenal syndrome. The aim of this paper is to describe the pathophysiology and clinical features of septic cardiorenal syndrome in light of the actual clinical and experimental evidence. In particular, the importance of systemic and intrarenal endothelial dysfunction, alterations of kidney perfusion, and myocardial function, organ “crosstalk” and ubiquitous inflammatory injury have been extensively reviewed in light of their role in cardiorenal syndrome etiology. Treatment includes early and targeted optimization of hemodynamics to reverse systemic hypotension and restore urinary output. In case of persistent renal impairment, renal replacement therapy may be used to remove cytokines and restore renal function.

  14. Glucocorticosteroids for sepsis

    DEFF Research Database (Denmark)

    Volbeda, M; Wetterslev, J; Gluud, C

    2015-01-01

    INTRODUCTION: Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light...... for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary......-adjusted CI 0.7-1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn. CONCLUSION: Evidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results...

  15. Sepsis: nieuwe inzichten, nieuwe definitie

    NARCIS (Netherlands)

    Wiersinga, W. J.; van Zanten, A. R. H.; Kaasjager, K. A.; van der Poll, T.

    2017-01-01

    - Incidence of sepsis is increasing, partly due to an ageing population, increased use of immunosuppressants, and antibiotic resistance. Sepsis survival has improved substantially, in part because of continuously improving intensive care and implementation of evidence-based guidelines.- Sepsis is

  16. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings......, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations...... of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality....

  17. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings......, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations...... of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality....

  18. Aetiology and Impact of Intra-abdominal Sepsis on Surgical ...

    African Journals Online (AJOL)

    An overview of intra-abdominal sepsis is necessary at this time with new experimental studies and audits on management outcomes. The understanding of the pathophysiology of the peritoneum in the manifestation of surgical sepsis and the knowledge of the source of pathogenic organisms which reach the peritoneal ...

  19. Síndrome de disfunção de múltiplos órgãos induzida por sepse: estudo experimental em ratos Sepsis inducing syndrome of multiple organ dysfunction: an experimental study in rats

    Directory of Open Access Journals (Sweden)

    João Batista de Area Lima

    2011-06-01

    Full Text Available RACIONAL: A principal causa de morte em pacientes com sepse em cirurgia é a síndrome de disfunção de múltiplos órgãos. Assim, modelos experimentais que simulem alterações orgânicas da sepse em humanos são necessários. OBJETIVO: Apresentar dois modelos que induzem a síndrome de disfunção de múltiplos órgãos e comparar as alterações induzidas por inoculação endovenosa de 36UE de lipopolissacarídeo ou célula viável de Escherichia coli, em relação à: mortalidade e sobrevivência; nível de lipopolissacarídeo; liberação de fator de necrose tumoral alfa; alterações hematológicas e das funções hepática e renal. MÉTODO: Este estudo teve duração de sete dias e utilizou-se nele 50 ratos Wistar machos, divididos em três grupos: controle, lipopolissacarídeo e Escherichia coli. Os grupos experimento eram inoculados e separados em dois subgrupos, com inoculação a cada 24 ou 48 horas. No sétimo dia eram procedidas coletas de sangue e análise histopatológica de fígado, rins e pulmões. RESULTADOS: Houve sobrevivência de dez animais no grupo controle; zero no bacteriano de 24 horas e seis no de 48 horas; dez no lipopolissacarídeo de 24 horas e seis no de 48 horas. Nos grupos experimentais, os níveis de lipopolissacarídeo, fator de necrose tumoral alfa, leucócitos, plaquetas, bastonetes e as alterações renais e hepáticas foram superiores ao grupo controle. Houve alterações histopatológicas no grupo bacteriano. CONCLUSÃO: Os dois modelos de sepse induziram síndrome de disfunção de múltiplos órgãos, contudo a administração de 36UE de endotoxina a cada 48 horas pode ser utilizada com vantagens sobre os demais por não induzir morte em número significativo durante o período de sete dias.BACKGROUND: The leading cause of death in patients with sepsis in surgery is syndrome of multiple organ dysfunction. Thus, experimental models that simulate organic changes of sepsis in humans are required. AIM: To

  20. 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

  1. Mechanism of the inhibitory effect of ghrelin in sepsis

    Directory of Open Access Journals (Sweden)

    Asha Jacob

    2010-02-01

    Full Text Available Asha Jacob, Rongqian Wu, Mian Zhou, Gene F Coppa, Ping WangDepartment of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, and The Feinstein Institute for Medical Research, Manhasset, NY, USAAbstract: Sepsis and septic shock are the leading causes of death in intensive care units. Approximately 40%–70% of the mortality is associated with severe sepsis and septic shock. Systemic antibiotic usage, surgical intervention, aggressive fluid resuscitation and careful monitoring are common measures currently used to treat sepsis. Despite the advances in the understanding of the pathophysiology of sepsis, very little progress has been made towards therapeutic interventions. Recently we have shown that ghrelin, a stomach-derived peptide which is an endogenous ligand for the growth hormone secretagogue receptor (GHSR-1a, is beneficial in attenuating the inflammatory response, organ injury and mortality in an experimental model of polymicrobial sepsis induced by cecal ligation and puncture (CLP. In this review, we describe the mechanism of action of ghrelin in sepsis, highlight the role ghrelin plays in attenuating the hepatic dysfunction induced by sepsis and septic shock and suggest in developing ghrelin as a potential therapy for sepsis.Keywords: ghrelin, sepsis, inhibition septic shock, GHSR-1a, cecal ligation

  2. Hemodynamic Support in Sepsis

    Directory of Open Access Journals (Sweden)

    Fatih Yildiz

    2014-04-01

    Full Text Available Sepsis is called systemic inflammatory response syndrome due to infection. When added to organs failure and perfusion abnormality is defined in severe sepsis, Hypotension that do not respond to fluid therapy is as defined septic shock. Fluid resuscitation is a most important parts of the treatment in patients with septic shock. Ongoing hypotension that despite of the adequate fluid therapy, vasopressor support initiation is required. Sepsis and septic shock, hemodynamic support is often understood as the hemodynamic support. The different approaches to the development of methods to track and objective comes up. Patients with severe sepsis and septic shock should be follow in the intensive care unit and rapid fluid replacement and effectual hemodynamic support should be provided.

  3. Gas tonometry for evaluation of gastrointestinal mucosal perfusion: experimental and clinical sepsis¹. part 2 Tonometria a gás para a avaliação da perfusão da mucosa gastrointestinal: sepse clínica e experimental. Parte 2

    Directory of Open Access Journals (Sweden)

    Eliezer Silva

    2002-09-01

    Full Text Available Substantial clinical and animal evidences indicate that the mesenteric circulatory bed, particularly the gut mucosa, is highly vulnerable to reductions in oxygen supply and prone to early injury in the course of hemodynamic changes induced by sepsis and septic shock. Gut hypoxia or ischemia is one possible contributing factor to gastrointestinal tract barrier dysfunction that may be associated with the development of systemic inflammatory response and multiple organ dysfunction syndrome, the principal cause of death after sepsis. Monitoring gut perfusion during experimental and clinical sepsis may provide valuable insights over new interventions and therapies highly needed to reduce multiple organ dysfunction and sepsis-related morbidity and mortality. We present our experience with gas tonometry as a monitor of the adequacy of gastrointestinal mucosal perfusion in experimental models sepsis and with the use of vasoactive agents for hemodynamic management in patients with septic shock.Evidências clínicas e experimentais substanciais indicam que o território circulatório mesentérico, principalmente na mucosa intestinal, é altamente vulnerável a redução na oferta de oxigênio e predisposto a lesão precoce na presença de alterações hemodinâmicas induzidas pela sepse e choque séptico. A hipóxia ou isquemia intestinal é um dos possíveis mecanismos contribuintes para a disfunção da barreira gastrointestinal que pode estar associada com o desenvolvimento da resposta inflamatória sistêmica e com a síndrome da disfunção de múltiplos órgãos, a principal causa comum de morte na sepse. Monitorar a perfusão intestinal na sepse experimental e clínica pode fornecer dados valiosos quanto a novas intervenções e tratamentos altamente necessários para reduzir disfunção de múltiplos órgãos e mortalidade extremamente elevadas na sepse. Apresentamos nossa experiência com a tonometria a gás como monitor da adequação da perfus

  4. Neonatal Sepsis in Haiti.

    Science.gov (United States)

    Boulos, Alexandre; Rand, Katherine; Johnson, Josh A; Gautier, Jacqueline; Koster, Michael

    2017-02-01

    Infections (including sepsis, meningitis, pneumonia and tetanus) stand as a major contributor to neonatal mortality in Haiti (22%). Infants acquire bacteria that cause neonatal sepsis directly from the mother's blood, skin or vaginal tract either before or during delivery. Nosocomial and environmental pathogens introduce further risk after delivery. The absence of cohesive medical systems and methods for collecting information limits the available data in countries such as Haiti. This study seeks to add more information on the burden of severe bacterial infections and their etiology in neonates of Haiti. Researchers conducted a secondary retrospective analysis of a de-identified database from the Neonatal Intensive Care Unit (NICU) at Nos Petit Frères et Soeurs-St. Damien Hospital (NPFS-SDH). Records from 1292 neonates admitted to the NICU at NPFS-SDH in Port-au-Prince Haiti from 2013 to 2015 were reviewed. Sepsis accounted for 708 of 1292 (54.8%) of all admissions to the NICU. Infants admitted for sepsis had a mortality rate of 23% (163 of 708 infants admitted for sepsis). The most common organism cultured was Streptococcus agalactiae, followed by Klebsiella pneumoniae, Pseudomonas aeroginusa, Enterobacter aerogenes, Staphylococcus aureus and Proteus mirabillis Failure to order or obtain a culture was associated with an increased fatality (odds ratio 2.4) for infants with sepsis. Resistance should be a concern when treating empirically. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Sepsis in frail patient

    Directory of Open Access Journals (Sweden)

    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

  6. Animal and human models for sepsis

    NARCIS (Netherlands)

    Schultz, Marc J.; van der Poll, Tom

    2002-01-01

    Several preclinical models for sepsis have been used in the last decades to successfully unravel the pathophysiologic processes during sepsis. Furthermore, these models for sepsis revealed promising immunomodulating agents for the treatment of sepsis. Nevertheless. several clinical trials evaluating

  7. Fast mixing hyperdynamic sampling

    OpenAIRE

    Sminchisescu, Cristian; Triggs, Bill

    2006-01-01

    Special issue on ECCV'02 papers; International audience; Sequential random sampling (‘Markov Chain Monte-Carlo') is a popular strategy for many vision problems involving multi-modal distributions over high-dimensional parameter spaces. It applies both to importance sampling (where one wants to sample points according to their ‘importance' for some calculation, but otherwise fairly) and to global-optimization (where one wants to find good minima, or at least good starting points for local mini...

  8. Hyperdynamics Importance Sampling

    OpenAIRE

    Sminchisescu, Cristian; Triggs, Bill

    2002-01-01

    International audience; Sequential random sampling (‘Markov Chain Monte-Carlo') is a popular strategy for many vision problems involving multimodal distributions over high-dimensional parameter spaces. It applies both to importance sampling (where one wants to sample points according to their ‘importance' for some calculation, but otherwise fairly) and to global optimization (where one wants to find good minima, or at least good starting points for local minimization, regardless of fairness)....

  9. Sepsis after elective ureteroscopy.

    Science.gov (United States)

    Bloom, Jonathan; Fox, Cristina; Fullerton, Sean; Matthews, Gerald; Phillips, John

    2017-10-01

    We sought to determine our rate of postoperative sepsis after ureteroscopy as well as identifying associative factors, common antibiotic practices along with culture data. Records of all patients who underwent elective ureteroscopy from 2010 to 2015 at an urban tertiary care facility were retrospectively reviewed. Factors thought to be associated with infection were collected, along with comorbidities depicted as Charlson Age-Adjusted Comorbidity Index (CAACI) and American Society of Anesthesia (ASA) score. Each patient's course was reviewed to determine if they were treated for postoperative sepsis as defined by standardized criteria. A total of 345 patients underwent elective ureteroscopy with 15 (4.3%) being treated for sepsis postoperatively. This resulted in an additional 5.33 ± 3.84 days of hospitalization per patient. The sepsis group grew three gram positive organisms and five multi-drug resistant (MDR) gram negatives while 7/15 (46.7%) had negative cultures. The most common preoperative antibiotics used in the sepsis group were cefazolin (60.0%), gentamicin (48.5%) and ciprofloxacin (20.0%). Univariate analysis showed prior endoscopic procedures, recent treatment for urinary tract infections (UTI), multiple comorbidities and longer operative times associated with sepsis. However, significant variables after multivariate analysis were treatment for UTI within the last month, (OR) 7.19 (2.25-22.99), p = 0.001. Patients with multiple comorbidities, prior endoscopic procedures, longer operative times and especially those recently treated for a urinary infection should be carefully monitored after ureteroscopy for signs of sepsis. Perioperative antibiotics in these patients should be selected to cover both MDR organisms and gram positives.

  10. Hydroxyethyl starch in sepsis

    DEFF Research Database (Denmark)

    Haase, Nicolai Rosenkrantz Segelcke

    2014-01-01

    patients with severe sepsis in the intensive care unit to fluid resuscitation with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate. The primary outcome measure was death or dialysis-dependency at 90 days after randomisation. Secondary outcomes described kidney function and serious adverse reactions....... Secondly, we systematically identified all randomised clinical trials comparing tetrastarch with either crystalloid or albumin in patients with sepsis and pooled their results in meta-analyses and trial sequential analyses. RESULTS: Of the 804 patients who underwent randomisation, 798 were included...... significant increased risk of any bleeding with HES vs. Ringer's acetate (relative risk 1.56, p=0.003). In the systematic review, we identified nine trials that randomised 3,456 patients with sepsis. In meta-analyses, tetrastarch vs. crystalloid or albumin lead to increased use of renal replacement therapy...

  11. Sepsis and Septic Shock Strategies.

    Science.gov (United States)

    Armstrong, Bracken A; Betzold, Richard D; May, Addison K

    2017-12-01

    Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  13. High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

    Directory of Open Access Journals (Sweden)

    Kuiper Jan

    2011-12-01

    Full Text Available Abstract Background To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI and resultant systemic inflammatory responses. Methods Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV with either a low tidal volume (Vt of 6 mL/kg and 5 cm H2O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis. Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D weight ratios, histological lung injury and plasma mediator concentrations were measured. Results Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed. Conclusions During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of

  14. CLINICAL RECOMMENDATIONS FOR DIAGNOSING SEPSIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    R. F. Tepaev

    2015-01-01

    Full Text Available Sepsis is one of the leading causes of child lethality. Timely diagnostics is the most important condition for treating sepsis successfully. This study contains analysis of recommendations on diagnosing the syndrome of systemic inflammatory response, sepsis, severe sepsis and septic shock of the Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012,published in 2013. The modern perceptions of systemic inflammation during sepsis and sterile inflammation are highlighted.

  15. [Sepsis masquerading as delirium].

    Science.gov (United States)

    Seifert, A; Hartog, C S; Zweigner, J; Schummer, W; Reinhart, K

    2017-11-01

    A previously healthy 60-year-old patient presented to the emergency department with severe headache, altered personality and fever. He was treated for bacterial meningitis with delirium of unknown cause but presumed to be due to alcohol withdrawal. Despite receiving the antibiotic therapy regimen recommended for bacterial meningitis the patient's condition rapidly deteriorated with profound delirium and tachypnea. The intensivist who was consulted immediately suspected sepsis-associated organ failure and admitted the patient to the intensive care unit (ICU). The blood culture was positive for Listeria. After 10 days the patient could be discharged from the ICU and ultimately recovered completely. In patients presenting with unexplained delirium or altered personality the suspicion of septic encephalopathy should always be considered. They should be admitted to the ICU and sepsis treatment should be initiated without delay.

  16. Sepsis and the heart.

    Science.gov (United States)

    Hunter, J D; Doddi, M

    2010-01-01

    Septic shock, the most severe complication of sepsis, accounts for approximately 10% of all admissions to intensive care. Our understanding of its complex pathophysiology remains incomplete but clearly involves stimulation of the immune system with subsequent inflammation and microvascular dysfunction. Cardiovascular dysfunction is pronounced and characterized by elements of hypovolaemic, cytotoxic, and distributive shock. In addition, significant myocardial depression is commonly observed. This septic cardiomyopathy is characterized by biventricular impairment of intrinsic myocardial contractility, with a subsequent reduction in left ventricular (LV) ejection fraction and LV stroke work index. This review details the myocardial dysfunction observed in adult septic shock, and discusses the underlying pathophysiology. The utility of using the regulatory protein troponin for the detection of myocardial dysfunction is also considered. Finally, options for the management of sepsis-induced LV hypokinesia are discussed, including the use of levosimendan.

  17. Vitamin D and sepsis

    OpenAIRE

    Kempker, Jordan A; Jenny E. Han; Tangpricha, Vin; Ziegler, Thomas R.; Martin, Greg S.

    2012-01-01

    Vitamin D insufficiency and sepsis are both highly prevalent worldwide problems and this article reviews the emerging science that is defining the intersections of these conditions. The importance of vitamin D’s role in skeletal health has long been understood but recent evidence is beginning to highlight its role in the functioning of other physiologic systems of the body. Basic science data reveal its integral role in local immune responses to pathogens and the systemic inflammatory pathway...

  18. HDL in sepsis - risk factor and therapeutic approach

    Directory of Open Access Journals (Sweden)

    Emily E Morin

    2015-10-01

    Full Text Available High-density lipoprotein (HDL is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 40-70% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI null mice as an HDL deficient model showed that mice lacking HDL are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an efficient therapy for sepsis. In this review, we discuss the roles of HDL in sepsis and summarize the efforts of using synthetic HDL as a potential therapy for sepsis.

  19. Surviving Sepsis: Taming a Deadly Immune Response

    Science.gov (United States)

    ... Issues Subscribe August 2014 Print this issue Surviving Sepsis Taming a Deadly Immune Response En español Send ... Mouth? Looking at Lupus Wise Choices Signs of Sepsis Sepsis can be hard to spot, because its ...

  20. Sepsis, severe sepsis and septic shock in adults and anaesthesia

    African Journals Online (AJOL)

    Unknown

    ... 90 beats/min; respiratory rate >20 breaths min; and white blood cell count > 12000 mm'3, 10% immature (band) forms. Severe sepsis: Sepsis associated with organ dysfunction, hypoperfusion or hypotension. Hypoperfusion and perfusion abnormalities may include but are not limited to, lactic acidosis,.

  1. Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

    Science.gov (United States)

    Bakalov, Veli; Amathieu, Roland; Triba, Mohamed N.; Clément, Marie-Jeanne; Reyes Uribe, Laura; Le Moyec, Laurence; Kaynar, Ata Murat

    2016-01-01

    Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. PMID:28009836

  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. Role of C5 Activation Products in Sepsis

    Directory of Open Access Journals (Sweden)

    Peter A. Ward

    2010-01-01

    Full Text Available Complement activation products are known to be generated in the setting of both experimental and human sepsis. C5 activation products (C5a anaphylatoxin and the membrane attack complex [MAC] C5b-9 are generated during sepsis following infusion of endotoxin, or after cecal ligation and puncture (CLP, which produces polymicrobial sepsis. C5a reacts with its receptors C5aR and C5L2 in a manner that creates the “cytokine storm”, and is associated with development of multiorgan failure (MOF. A number of other complications arising from the interaction of C5a with its receptors include apoptosis of lymphoid cells, loss of innate immune functions of neutrophils (PMNs, polymorphonuclear leukocytes, cardiomyopathy, disseminated intravascular coagulation, and complications associated with MOF. Neutralization of C5a in vivo or absence/blockade of C5a receptors greatly reduces the adverse events in the setting of sepsis, markedly attenuates MOF, and greatly improves survival. Regarding the possible role of C5b-9 in sepsis, the literature is conflicting. Some studies suggest that C5b-9 is protective, while other studies suggest the contrary. Clearly, in human sepsis, C5a and its receptors may be logical targets for interception.

  4. 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.

  5. [Aberrant bone remodeling during sepsis.

    Science.gov (United States)

    Terashima, Asuka

    Sepsis is a systemic inflammatory response syndrome that occurs upon severe bacterial infection. Although the development of early treatment for sepsis improves the survival rate of sepsis patients, in the subacute phase, certain patients suffer from secondary infection due to immunosuppression. It has been reported that one of the causes of the immunocompromised state during sepsis is lymphopenia. However, the underlying mechanisms are not well understood. We found that acute inflammation induced the immunodeficiency caused by the reduction of the numbers of peripheral lymphocytes and common lymphoid progenitors(CLPs)in the bone marrow, which was associated with a dramatic decrease in the osteoblast number. Osteoblast-specific deletion of IL-7 provided evidence for the role of osteoblasts in the regulation of lymphopoiesis in systemic inflammation. An acute loss of osteoblasts in sepsis induced the disturbance of lymphocyte homeostasis, resulting in immunodeficiency.

  6. The endothelium in sepsis: source of and a target for inflammation

    NARCIS (Netherlands)

    Hack, C. E.; Zeerleder, S.

    2001-01-01

    To discuss a possible role of the endothelium in sepsis. Studies published in biomedical journals and our own experimental results. Studies on endothelial mechanisms in the context of sepsis. Changes in endothelial cells on activation by inflammatory stimuli are reviewed briefly; potential

  7. Effects of Ecballium elaterium on brain in a rat model of sepsis ...

    African Journals Online (AJOL)

    Demet Arslan

    2017-08-31

    Aug 31, 2017 ... Long-term memory deficit and neuronal loss was seen in experimental models, similar to signs in patients with sepsis [30]. Our study also showed higher neuronal damage, pericellular/perivascular edema and inflammatory cell infiltration score in the sepsis group. This score was significantly lowered in.

  8. Anti-Inflammatory Effect of Momordica Charantia in Sepsis Mice

    Directory of Open Access Journals (Sweden)

    Che-Yi Chao

    2014-08-01

    Full Text Available Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe, a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPARα and PPARγ. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%, moderate (2%, and high (10% ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-α tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-κB, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis.

  9. Corticosteroids for treating sepsis.

    Science.gov (United States)

    Annane, Djillali; Bellissant, Eric; Bollaert, Pierre Edouard; Briegel, Josef; Keh, Didier; Kupfer, Yizhak

    2015-12-03

    Sepsis occurs when an infection is complicated by organ failures as defined by a sequential organ failure assessment (SOFA) score of two or higher. Sepsis may be complicated by impaired corticosteroid metabolism. Giving corticosteroids may benefit patients. The original review was published in 2004 and was updated in 2010 and again in 2015. To examine the effects of corticosteroids on death at one month in patients with sepsis, and to examine whether dose and duration of corticosteroids influence patient response to this treatment. We searched the Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (October 2014), EMBASE (October 2014), Latin American Caribbean Health Sciences Literature (LILACS; October 2014) and reference lists of articles, and we contacted trial authors. The original searches were performed in August 2003 and in October 2009. We included randomized controlled trials of corticosteroids versus placebo or supportive treatment in patients with sepsis. All review authors agreed on the eligibility of trials. One review author extracted data, which were checked by the other review authors, and by the primary author of the paper when possible. We obtained some missing data from trial authors. We assessed the methodological quality of trials. We identified nine additional studies since the last update, for a total of 33 eligible trials (n = 4268 participants). Twenty-three of these 33 trials were at low risk of selection bias, 22 were at low risk of performance and detection bias, 27 were at low risk of attrition bias and 14 were at low risk of selective reporting.Corticosteroids reduced 28-day mortality (27 trials; n = 3176; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.76 to 1.00; P value = 0.05, random-effects model). The quality of evidence for this outcome was downgraded from high to low for imprecision (upper limit of 95% CI = 1) and for inconsistency (significant heterogeneity across trial results). Heterogeneity was

  10. The Changing Epidemiology and Definitions of Sepsis

    Science.gov (United States)

    Kempker, Jordan A.; Martin, Greg S.

    2016-01-01

    Synopsis This review begins with a description of the trends in the incidence of and mortality from sepsis in the United States and globally. Then we discuss the known factors associated with increased risk for the development of sepsis. Finally, we discuss the limitations of the current clinical definition of sepsis and the clinical correlations of the current epidemiology of sepsis. PMID:27229635

  11. Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep.

    Science.gov (United States)

    Murakami, Kazunori; McGuire, Roy; Cox, Robert A; Jodoin, Jeffrey M; Bjertnaes, Lars J; Katahira, Jiro; Traber, Lillian D; Schmalstieg, Frank C; Hawkins, Hal K; Herndon, David N; Traber, Daniel L

    2002-09-01

    Pseudomonas pneumonia is a common complication of smoke inhalation injury. Airway casts formed from clotted mucous occur frequently in this condition. A recent report shows that intravenous heparin improves oxygenation and reduces lung damage in a sheep model of smoke inhalation. We hypothesized that nebulized heparin could be an effective means of reducing cast formation. Female sheep (n = 19) were surgically prepared for a study of acute lung injury (ALI). After a tracheotomy, 48 breaths of cotton smoke (heparin-nebulized group (n = 5; animals received aerosolized heparin [10,000 I.U.] 1 h after the bacterial instillation and subsequently every 4 h thereafter), an intravenous heparin group (n = 5,300 U/kg/23 h, infusion was started 1 h after the injury), a saline-nebulization group (n = 5; animals received inhaled nebulized saline), and a sham injury group (n = 4, treated in the same fashion, but no injury). The animals were sacrificed after 24 h of mechanical ventilation, and lung samples were harvested. Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes and a corresponding drop in PaO2. These changes were significantly attenuated in the heparin groups. Histological changes consisting of cellular infiltrates, lung edema, congestion, and cast formation were reduced by heparin. These data suggest that nebulized inhaled heparin is a beneficial therapy for sepsis-induced ALI.

  12. Neonatal Sepsis and Neutrophil Insufficiencies

    Science.gov (United States)

    Melvan, John Nicholas; Bagby, Gregory J.; Welsh, David A.; Nelson, Steve; Zhang, Ping

    2011-01-01

    Sepsis has continuously been a leading cause of neonatal morbidity and mortality despite current advances in chemotherapy and patient intensive care facilities. Neonates are at high risk for developing bacterial infections due to quantitative and qualitative insufficiencies of innate immunity, particularly granulocyte lineage development and response to infection. Although antibiotics remain the mainstay of treatment, adjuvant therapies enhancing immune function have shown promise in treating sepsis in neonates. This chapter reviews current strategies for the clinical management of neonatal sepsis and analyzes mechanisms underlying insufficiencies of neutrophil defense in neonates with emphasis on new directions for adjuvant therapy development. PMID:20521927

  13. Sepsis por shigella flexneri

    Directory of Open Access Journals (Sweden)

    César Cabrera C

    2005-04-01

    Full Text Available Se presenta un caso raro de sepsis por Shigella flexneri en una paciente de 45 años de edad quien estando hospitalizada para el estudio de un tumor cerebral, requirió el uso de manitol y dosis altas de corticoides; luego de ello presenta deposiciones líquidas con moco y sangre, desarrolla síndrome de respuesta inflamatoria sistémica, luego se aísla Shigella flexneri en el hemocultivo; recibió tratamiento antibiótico con ciprofloxacina. Se describen las características del caso y se comenta de acuerdo con la revisión de literatura.

  14. Moraxella catarrhalis sepsis

    Directory of Open Access Journals (Sweden)

    Paola Gualdi

    2008-06-01

    Full Text Available Moraxella catarrhalis is a Gram-negative aerobic diplococcus, commensal of the oro-pharingeal cavity, actually playing an emerging role in the upper respiratory tract infections together with Streptococcus pneumoniae and Haemophilus influenzae. This study reports the case of a twoyearold child who was admitted into hospital with fever, headache and vomit. The chest radiograph showed signs of basal lung involvementmaking the clinical suspicion of bacterial infectionlikely. From blood culture a Moraxella catarrhalis strain was isolated. In young children M. catarrhalis is known to cause otitis media and sinusitis, but only rarely bacteremia. In this case the child showed a clinical picture of lung infection and consequent sepsis due to M. catarrhalis.

  15. Disseminated intravascular coagulation in sepsis

    NARCIS (Netherlands)

    Zeerleder, Sacha; Hack, C. Erik; Wuillemin, Walter A.

    2005-01-01

    Disseminated intravascular coagulation is a frequent complication of sepsis. Coagulation activation, inhibition of fibrinolysis, and consumption of coagulation inhibitors lead to a procoagulant state resulting in inadequate fibrin removal and fibrin deposition in the microvasculature. As a

  16. Radiologic findings of neonatal sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong [Sansung Medical Center, Seoul (Korea, Republic of)

    1997-06-01

    To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment.

  17. The Coagulant Response in Sepsis

    NARCIS (Netherlands)

    Levi, Marcel

    2008-01-01

    Sepsis is often associated with systemic intravascular activation of coagulation, potentially leading to widespread microvascular deposits of fibrin, and thereby contributing to multiple organ dysfunction. A complex interaction exists between activation of inflammatory systems and the initiating and

  18. Endoplasmic Reticulum Stress in Sepsis

    Science.gov (United States)

    Khan, Mohammad Moshahid; Yang, Weng-Lang; Wang, Ping

    2015-01-01

    Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units (ICU). Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with the sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. Under the stress and inflammation condition, ER loses the homeostasis in its function, which is termed as ER stress. During ER stress, unfolded protein response (UPR) is activated to restore ER function to its normal balance. However, once the stress is beyond the compensatory capacity of UPR or protracted, the apoptosis would be initiated by triggering cell injuries, even to cell death. As such, ER stress and UPR are reported to be implicated in several pathological and inflammatory conditions. Although the detrimental role of ER stress during infections has been demonstrated, there is growing evidences that ER stress participate in the pathogenesis of sepsis. In this review, we summarize the current research in the context of ER stress and UPR signaling associated with sepsis and its related clinical conditions, such as trauma- hemorrhage, and ischemia/reperfusion (I/R) injury. We also discuss the potential implication of ER stress as a novel therapeutic target and prognostic marker in patients with sepsis. PMID:26125088

  19. [Is a different view on the pathophysiology of sepsis the key for novel therapeutic options?].

    Science.gov (United States)

    Schlegel, N; Flemming, S; Meir, M; Germer, C-T

    2014-08-01

    Sepsis remains a critical problem in virtually all fields of clinical medicine. Despite intensive scientific and clinical efforts no significant progress has emerged in the fight against sepsis mortality. Solely the algorithm of the "surviving sepsis campaign" has proven to result in significantly enhanced survival of sepsis patients when consequently adopted. Novel research in the field of the complex immunological alterations in sepsis suggests that ongoing immunosuppression is the critical determinant underlying sepsis mortality. Therefore, it was proposed that immunostimulation might be a successful approach to improve outcome in individually selected patients. Others favor a different view on the pathophysiology of sepsis and support the notion that the manifestation of organ failure may be the dominant therapeutic target. Due to the fact that breakdown of the microcirculation and disruption of the microvascular barrier are critical events preceding organ failure, experimental therapeutic efforts to address these events led to promising results. Taken together, in view of the many initially promising experimental data and the failure to translate them into successful clinical therapies, a different view on the pathophysiology of sepsis is warranted to obtain the key for novel therapeutic options.

  20. Beyond sepsis : activated protein C and ischemia-reperfusion injury

    NARCIS (Netherlands)

    Levi, Marcel; Choi, Goda; Schoots, Ivo; Schultz, Marcus; van der Poll, Tom

    OBJECTIVE: To review potential clinical situations beyond sepsis in which activated protein C might be an effective treatment. DATA SOURCE: Published articles between 1970 and 2003 on experimental and clinical studies of activation of both coagulation and inflammation in various disease states. DATA

  1. Neonatal Sepsis and Inflammatory Mediators

    Science.gov (United States)

    Reis Machado, Juliana; Soave, Danilo Figueiredo; da Silva, Marcos Vinícius; de Menezes, Liliana Borges; Etchebehere, Renata Margarida; Monteiro, Maria Luiza Gonçalves dos Reis; Antônia dos Reis, Marlene; Corrêa, Rosana Rosa Miranda; Celes, Mara Rúbia Nunes

    2014-01-01

    Neonatal sepsis is a major cause of morbidity and mortality and its signs and symptoms are nonspecific, which makes the diagnosis difficult. The routinely used laboratory tests are not effective methods of analysis, as they are extremely nonspecific and often cause inappropriate use of antibiotics. Sepsis is the result of an infection associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. Cytokines are potent inflammatory mediators and their serum levels are increased during infections, so changes from other inflammatory effector molecules may occur. Although proinflammatory and anti-inflammatory cytokines have been identified as probable markers of neonatal infection, in order to characterize the inflammatory response during sepsis, it is necessary to analyze a panel of cytokines and not only the measurement of individual cytokines. Measurements of inflammatory mediators bring new options for diagnosing and following up neonatal sepsis, thus enabling early treatment and, as a result, increased neonatal survival. By taking into account the magnitude of neonatal sepsis, the aim of this review is to address the role of cytokines in the pathogenesis of neonatal sepsis and its value as a diagnostic criterion. PMID:25614712

  2. Severe sepsis in older adults.

    Science.gov (United States)

    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.

  3. Stem Cell-based Therapies for Sepsis.

    Science.gov (United States)

    Keane, Colm; Jerkic, Mirjana; Laffey, John G

    2017-12-01

    Sepsis is a life-threatening syndrome resulting in shock and organ dysfunction stemming from a microbial infection. Sepsis has a mortality of 40% and is implicated in half of all in-hospital deaths. The host immune response to microbial infection is critical, with early-phase sepsis characterized by a hyperinflammatory immune response, whereas the later phase of sepsis is often complicated by suppression. Sepsis has no treatment, and management remains supportive.Stem cells constitute exciting potential therapeutic agents for sepsis. In this review, we examine the rationale for stem cells in sepsis, focusing on mesenchymal stem/stromal cells, which currently demonstrate the greatest therapeutic promise. We examine the preclinical evidence base and evaluate potential mechanisms of action of these cells that are important in the setting of sepsis. We discuss early-phase clinical trials and critically appraise translational barriers to the use of mesenchymal stem/stromal cells in patients with sepsis.

  4. 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

  5. RX-207, a Small Molecule Inhibitor of Protein Interaction with Glycosaminoglycans (SMIGs), Reduces Experimentally Induced Inflammation and Increases Survival Rate in Cecal Ligation and Puncture (CLP)-Induced Sepsis.

    Science.gov (United States)

    Juhas, Stefan; Harris, Nicholas; Il'kova, Gabriela; Rehák, Pavol; Zsila, Ferenc; Yurgenzon Kogan, Faina; Lahmy, Orly; Zhuk, Regina; Gregor, Paul; Koppel, Juraj

    2018-02-01

    The fused quinazolinone derivative, RX-207, is chemically and functionally related to small molecule inhibitors of protein binding to glycosaminoglycans (SMIGs). Composed of a planar aromatic amine scaffold, it inhibits protein binding to glycosaminoglycans (GAGs). RX-207 reduced neutrophil migration in thioglycollate-induced peritonitis (37%), inhibited carrageenan-induced paw edema (32%) and cerulein-induced pancreatitis (28%), and increased animal survival in the mouse model of cecal ligation and puncture (CLP)-induced sepsis (60%). The mechanism of RX-207 action, analyzed by UV spectroscopy, confirmed that which was elucidated for chemically related anti-inflammatory SMIGs. RX-207 binding to cell surface GAGs can account for the inhibition of neutrophil recruitment via the micro-vasculature and as a consequence, the reduction of neutrophil mediated tissue damage in the animal models of inflammation and improved survival of mice in CLP-induced sepsis.

  6. 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.

  7. Translational research in the development of novel sepsis therapeutics: logical deductive reasoning or mission impossible?

    Science.gov (United States)

    Opal, Steven M; Patrozou, Eleni

    2009-01-01

    The successful translation of promising research findings from basic research laboratories into useful clinical products for the management of septic patients has proven to be a daunting challenge. The complexity and variability of the clinical entity referred to as sepsis makes it intrinsically difficult to model preclinical systems and predict efficacy of potentially useful, experimental, therapeutic agents. Technological innovations in microarrays, microfluidics, and nanotechnology make it feasible to study the evolution of sepsis in small animal models in considerable detail. The recognized limitations of standard preclinical platforms used to study sepsis have lead to innovative approaches to study sepsis in silico, and in more complex and clinically more valid ex vivo tissue perfusion models and animal systems. It is abundantly clear that sepsis researchers need to do a better job informing clinicians about the possible benefits and potential risks of new treatment interventions as they traverse the gap between the bench and the bedside.

  8. Properdin levels in human sepsis

    Directory of Open Access Journals (Sweden)

    Cordula M Stover

    2015-02-01

    Full Text Available Properdin is a normal serum protein which increases the production of complement activation products by binding to C3b integral to convertase complexes and amplifying their activity at the site of activation. Thereby, it can aid in the resolution of infection but also contribute to tissue damage. In human sepsis, circulating complement C3 concentrations are decreased, though C3 is described as a positive acute phase reactant. However, properdin levels in human sepsis have not been reported. In this study, serum from 81 critically ill patients (predominately abdominal and respiratory sepsis were analysed for properdin levels at defined points of their stay in the Intensive Care Unit (ICU and compared with 61 age and sex-matched healthy volunteers. Properdin concentrations were significantly decreased in patients with sepsis on admission to ICU, but increased after clinical recovery to exceed levels observed in healthy volunteers. Properdin concentrations at ICU admission were decreased in non-survivors of sepsis compared to survivors, but this did not correlate with APACHE II score. However, pathologically low properdin levels (<7 microg/ml were related to increased duration of treatment.

  9. Deficiency of Bid protein reduces sepsis-induced apoptosis and inflammation, while improving septic survival.

    Science.gov (United States)

    Chung, Chun-Shiang; Venet, Fabienne; Chen, Yaping; Jones, Leslie N; Wilson, Douglas C; Ayala, Carol A; Ayala, Alfred

    2010-08-01

    Increased apoptotic cell death is believed to play a pathological role in patients with sepsis and experimental animals. Apoptosis can be induced by either a cell death receptor (extrinsic) or a mitochondrial (intrinsic) pathway. Bid, a proapoptotic member of the Bcl-2 family, is thought to mediate the cross talk between the extrinsic and intrinsic pathways of apoptosis; however, little is known about the action of Bid in the development of apoptosis and organ-specific tissue damage/cell death as seen in polymicrobial sepsis. Our results show that after the onset of sepsis, tBid (the active form of Bid) is significantly increased in mitochondrial fractions of the thymus, spleen, Peyer patches, and liver, and that Fas or FasL deficiency blocks Bid activation in various tissues after septic challenge. Increased Bid activation is correlated with increased active caspase-3, caspase-9, and apoptosis during sepsis. Bid-deficient mice exhibit significantly reduced apoptosis in the thymus, spleen, and Peyer patches compared with background mice after sepsis. Furthermore, Bid-deficient mice had significantly reduced systemic and local inflammatory cytokine levels and improved survival after sepsis. These data support not only the contribution of Bid to sepsis-induced apoptosis and the onset of septic morbidity/mortality, but also the existence of a bridge between extrinsic apoptotic signals, e.g., FasL:Fas, TNF:TNFR, and so on, and the intrinsic mitochondrial pathway via Bid-tBid activation during sepsis.

  10. [SOMETHING ABOUT DEFINITION AND EPIDEMIOLOGY OF SEPSIS].

    Science.gov (United States)

    Cavrić, G; Nassabain, K; Prkačin, I; Hamp, D Bartolek

    2015-09-01

    The prevalence of sepsis continues to increase, although, thanks to the efforts of the campaigns and the development of guidelines for sepsis treatment, the fatality rates have diminished, however, the sepsis total mortality is growing due to increased morbidity. Sepsis should be considered as an emergency almost similar to acute myocardial infarction. With regard to the high prevalence and high mortality rate, it is important to improve the definition of sepsis. This definition is also important in different researches, as well as in the application of the results in daily practice. In January 2014, at the 43rd Annual Congress of Society of Critical Care Medicine in San Francisco, the work on establishing a new definition of sepsis was started. New definition of sepsis probably would represent what is known today as severe sepsis. The new definition could probably be accomplished during 2015.

  11. 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 fentanyl (P fentanyl, whereas...

  12. Hyperdynamic CSF motion profiles found in idiopathic normal pressure hydrocephalus and Alzheimer's disease assessed by fluid mechanics derived from magnetic resonance images.

    Science.gov (United States)

    Takizawa, Ken; Matsumae, Mitsunori; Hayashi, Naokazu; Hirayama, Akihiro; Yatsushiro, Satoshi; Kuroda, Kagayaki

    2017-10-18

    Magnetic resonance imaging (MRI) does not only ascertain morphological features, but also measures physiological properties such as fluid velocity or pressure gradient. The purpose of this study was to investigate cerebrospinal fluid (CSF) dynamics in patients with morphological abnormalities such as enlarged brain ventricles and subarachnoid spaces. We used a time-resolved three dimensional phase contrast (3D-PC) MRI technique to quantitatively evaluate CSF dynamics in the Sylvian aqueduct of healthy elderly individuals and patients with either idiopathic normal pressure hydrocephalus (iNPH) or Alzheimer's disease (AD) presenting with ventricular enlargement. Nineteen healthy elderly individuals, ten iNPH patients, and seven AD patients (all subjects ≥ 60 years old) were retrospectively evaluated 3D-PC MRI. The CSF velocity, pressure gradient, and rotation in the Sylvian aqueduct were quantified and compared between the three groups using Kolmogorov-Smirnov and Mann-Whitney U tests. There was no statistically significant difference in velocity among the three groups. The pressure gradient was not significantly different between the iNPH and AD groups, but was significantly different between the iNPH group and the healthy controls (p < 0.001), and similarly, between the AD group and the healthy controls (p < 0.001). Rotation was not significantly different between the iNPH and AD groups, but was significantly different between the iNPH group and healthy controls (p < 0.001), and similarly, between the AD group and the healthy controls (p < 0.001). Quantitative analysis of CSF dynamics with time resolved 3D-PC MRI revealed differences and similarities in the Sylvian aqueduct between healthy elderly individuals, iNPH patients, and AD patients. The results showed that CSF motion is in a hyperdynamic state in both iNPH and AD patient groups compared to healthy elderly individuals, and that iNPH patients and AD patients display similar CSF motion profiles.

  13. PIRO concept: staging of sepsis.

    Science.gov (United States)

    Rathour, S; Kumar, S; Hadda, V; Bhalla, A; Sharma, N; Varma, S

    2015-01-01

    Sepsis is common presenting illness to the emergency services and one of the leading causes of hospital mortality. Researchers and clinicians have realized that the systemic inflammatory response syndrome concept for defining sepsis is less useful and lacks specificity. The predisposition, infection (or insult), response and organ dysfunction (PIRO) staging of sepsis similar to malignant diseases (TNM staging) might give better information. A prospective observational study was conducted in emergency medical services attached to medicine department of a tertiary care hospital in Northern India. Patients with age 18 years or more with proven sepsis were included in the first 24 hours of the diagnosis. Two hundred patients were recruited. Multivariate logistic regression analysis was done to assess the factors that predicted in-hospital mortality. Two hundred patients with proven sepsis, admitted to the emergency medical services were analysed. Male preponderance was noted (M: F ratio = 1.6:1). Mean age of study cohort was 50.50 ± 16.30 years. Out of 200 patients, 116 (58%) had in-hospital mortality. In multivariate logistic regression analysis, the factors independently associated with in-hospital mortality for predisposition component of PIRO staging were age >70 years, chronic obstructive pulmonary disease, chronic liver disease, cancer and presence of foley's catheter; for infection/ insult were pneumonia, urinary tract infection and meningitis/encephalitis; for response variable were tachypnea (respiratory rate >20/minute) and bandemia (band >5%). Organ dysfunction variables associated with hospital mortality were systolic blood pressure system as a predictor of in-hospital mortality was 0.94. This study finds PIRO staging as an important tool to stratify and prognosticate hospitalised patients with sepsis at a tertiary care center. The simplicity of score makes it more practical to be used in busy emergencies as it is based on four easily assessable components.

  14. Galactosemia presenting as recurrent sepsis.

    Science.gov (United States)

    Rathi, Narendra; Rathi, Akanksha

    2011-12-01

    Galactosemia is a treatable metabolic disorder caused by the deficiency of enzyme galactose-1-phosphate uridyl transferase (GALT) and inherited as an autosomal recessive trait. A case of neonate manifesting with recurrent Escherichia coli sepsis is presented here which turned out to be a classic galactosemia. No other common presenting features were observed in this infant except cataract on slit lamp examination. To the best of our knowledge, there is no case of galactosemia reported in literature which presented with recurrent neonatal sepsis without hepatomegaly, hyperbilirubinemia, bleeding disorder, vomiting, diarrhea, failure to thrive, hypoglycemia, coagulopathy, hemolysis or renal tubular acidosis.

  15. Role of fibrinolysis in sepsis.

    Science.gov (United States)

    Gando, Satoshi

    2013-06-01

    Sepsis, defined as infection-induced systemic inflammatory response syndrome, invariably leads to hemostatic abnormalities ranging from insignificant coagulopathy to disseminated intravascular coagulation (DIC). The inflammation-induced activation of coagulation, the downregulation of physiologic anticoagulant pathways, and impairment of fibrinolysis play a pivotal role in the pathogenesis of microvascular fibrin thrombosis and multiple organ dysfunction syndrome (MODS) in DIC associated with sepsis. The balance between tissue plasminogen activator and plasminogen activator inhibitor-1 mainly regulates fibrinolytic activity. Thrombin-activatable fibrinolysis inhibitor and neutrophil elastase also modulate fibrinolysis. Dynamic changes in these molecules are deeply involved in the pathomechanisms of the impairment of fibrinolysis, leading to MODS in DIC associated with sepsis. Evidence indicates that physical entrapment of bacteria by fibrin at the site of infection may limit their capacity to disseminate into nearby tissues, organs, and systemic circulation. Under this circumstance, impairment of fibrinolysis has protective role in the host defense. Given the protective and pathologic potential of fibrinolysis during sepsis, therapeutics that control DIC as a systemic syndrome, while maintaining the host defense at the infectious foci, are required for the protection against both the development of MODS and for the host defense mechanisms. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. Practical Considerations in Sepsis Resuscitation.

    Science.gov (United States)

    Long, Brit; Koyfman, Alex; Modisett, Katharine L; Woods, Christian J

    2017-04-01

    Sepsis is a common condition managed in the emergency department, and the majority of patients respond to resuscitation measures, including antibiotics and i.v. fluids. However, a proportion of patients will fail to respond to standard treatment. This review elucidates practical considerations for management of sepsis in patients who fail to respond to standard treatment. Early goal-directed therapy revolutionized sepsis management. However, there is a paucity of literature that provides a well-defined treatment algorithm for patients who fail to improve with therapy. Refractory shock can be defined as continued patient hemodynamic instability (mean arterial pressure, ≤ 65 mm Hg, lactate ≥ 4 mmol/L, altered mental status) after adequate fluid loading (at least 30 mL/kg i.v.), the use of two vasopressors (with one as norepinephrine), and provision of antibiotics. When a lack of improvement is evident in the early stages of resuscitation, systematically considering source control, appropriate volume resuscitation, adequate antimicrobial coverage, vasopressor selection, presence of metabolic pathology, and complications of resuscitation, such as abdominal compartment syndrome and respiratory failure, allow emergency physicians to address the entire clinical scenario. The care of sepsis has experienced many changes in recent years. Care of the patient with sepsis who is not responding appropriately to initial resuscitation is troublesome for emergency physicians. This review provides practical considerations for resuscitation of the patient with septic shock. When a septic patient is refractory to standard therapy, systematically evaluating the patient and clinical course may lead to improved outcomes. Published by Elsevier Inc.

  17. Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting.

    Directory of Open Access Journals (Sweden)

    Sandra Christina Pereira Lima Shiramizo

    Full Text Available BACKGROUND: The Surviving Sepsis Campaign (SSC guidelines for the management of severe sepsis (SS and septic shock (SSh have been recommended to reduce morbidity and mortality. MATERIALS AND METHODS: A quasi-experimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize SS and SSh shock patients' clinical outcomes were performed by applying sepsis bundles (6- and 24-hour in May 2006. We compared bundle compliance and patient outcomes before (July 2005-April 2006 and after (May 2006-December 2009 implementation of the interventions. RESULTS: A total of 564 SS and SSh patients were identified. Prior to the intervention, compliance with the 6 hour-sepsis resuscitation bundle was only 6%. After the intervention, compliance was as follows: 8.2% from May to December 2006, 9.3% in 2007, 21.1% in 2008 and 13.7% in 2009. For the 24 hour-management bundle, baseline compliance was 15.0%. After the intervention, compliance was 15.1% from May to December 2006, 21.4% in 2007, 27.8% in 2008 and 44.4% in 2009. The in-hospital mortality was 54.0% from July 2005 to April 2006, 41.1% from May to December 2006, 39.3% in 2007, 41.4% in 2008 and 16.2% in 2009. CONCLUSION: These results suggest reducing SS and SSh patient mortality is a complex process that involves multiple performance measures and interventions.

  18. Streptococcus milleri and surgical sepsis.

    Science.gov (United States)

    Tresadern, J. C.; Farrand, R. J.; Irving, M. H.

    1983-01-01

    For many years Viridans streptococci have been considered as commensal organisms in a wide variety of sites in the human body and only regarded as significant pathogens in subacute bacterial endocarditis. However, in recent years some reports have suggested that a particular species, Streptococcus milleri, can be a virulent pathogen, producing life-threatening sepsis particularly in surgical patients. We review here our experience of this organism in 23 general surgical patients over a 3 year period, and postulate that prophylactic use of antibiotic combinations such as gentamicin and metronidazole in patients undergoing colo-rectal surgery may be a factor promoting its emergence as a significant pathogen. Patients with established sepsis due to Streptococcus milleri should be considered for long-term antibiotic therapy as part of the treatment of their abscesses. PMID:6830135

  19. Molecular basics of sepsis developement.

    Science.gov (United States)

    Jedynak, Monika; Siemiątkowski, Andrzej; Rygasiewicz, Karolina

    2012-01-01

    Bacterial infections and sepsis remain major causes of morbidity and mortality in intensive care units. The normal host response to infection is a complex process that serves to localise and control the invasion of microbes and to repair injured tissue. Local inflammatory processes are regulated through the production of cytokines by macrophages. In some cases, mediator release exceeds the boundaries of the local environment and results in the development of sepsis. It is well known that the innate immune system plays a crucial role in preventing microbial invasion. The human innate immune system consists of genetically programmed defence mechanisms that are directed against molecular components found only in microorganisms. Understanding the complexity of early response to infection with respect to innate immune response is required for the future development of drugs that will effectively control infectious diseases.

  20. Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation

    Science.gov (United States)

    Herrmann, I. K.; Bertazzo, S.; O'Callaghan, D. J. P.; Schlegel, A. A.; Kallepitis, C.; Antcliffe, D. B.; Gordon, A. C.; Stevens, M. M.

    2015-08-01

    Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions. Electronic supplementary information (ESI) available: Fig. S1: Markers of inflammation and microvesicle characteristics in patient plasma samples, Fig. S2: Experimental sepsis model, Table S1: Patient characteristics. Table S2: Inclusion/exclusion criteria. See DOI: 10.1039/c5nr01851j

  1. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012!' Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings

  2. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    NARCIS (Netherlands)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need

  3. Lactic acidosis in pediatric sepsis

    OpenAIRE

    Корсунов, Володимир Анатолійович

    2015-01-01

    Aim. To determine the leading mechanisms of lactic acidosis course it is conducted a detailed analysis of scientific papers on this issue, and on the basis of modern scientific basis to conduct the study of the state of hemodynamics, metabolism and acid-base balance in pediatric sepsis.Methods. To achieve this aim it was used to identify indicators of central and organ hemodynamics by Doppler ultrasound, were studied the ABB indicators of central venous and arterial blood electrolytes, creati...

  4. Sepsis: Medical errors in Poland.

    Science.gov (United States)

    Rorat, Marta; Jurek, Tomasz

    2016-01-01

    Health, safety and medical errors are currently the subject of worldwide discussion. The authors analysed medico-legal opinions trying to determine types of medical errors and their impact on the course of sepsis. The authors carried out a retrospective analysis of 66 medico-legal opinions issued by the Wroclaw Department of Forensic Medicine between 2004 and 2013 (at the request of the prosecutor or court) in cases examined for medical errors. Medical errors were confirmed in 55 of the 66 medico-legal opinions. The age of victims varied from 2 weeks to 68 years; 49 patients died. The analysis revealed medical errors committed by 113 health-care workers: 98 physicians, 8 nurses and 8 emergency medical dispatchers. In 33 cases, an error was made before hospitalisation. Hospital errors occurred in 35 victims. Diagnostic errors were discovered in 50 patients, including 46 cases of sepsis being incorrectly recognised and insufficient diagnoses in 37 cases. Therapeutic errors occurred in 37 victims, organisational errors in 9 and technical errors in 2. In addition to sepsis, 8 patients also had a severe concomitant disease and 8 had a chronic disease. In 45 cases, the authors observed glaring errors, which could incur criminal liability. There is an urgent need to introduce a system for reporting and analysing medical errors in Poland. The development and popularisation of standards for identifying and treating sepsis across basic medical professions is essential to improve patient safety and survival rates. Procedures should be introduced to prevent health-care workers from administering incorrect treatment in cases. © The Author(s) 2015.

  5. Apelin attenuates postburn sepsis via a phosphatidylinositol 3-kinase/protein kinase B dependent mechanism: A randomized animal study

    National Research Council Canada - National Science Library

    Luo, Keqin; Long, Huibao; Xu, Bincan; Luo, Yanling

    2015-01-01

    This study aims to investigate whether apelin would regulate inflammatory response and promote survival in an experimental burn sepsis model through a phosphatidylinositol 3-kinase/protein kinase B dependent pathway...

  6. Sepsis-Induced Cardiomyopathy: Mechanisms and Treatments

    Directory of Open Access Journals (Sweden)

    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.

  7. Deregulation of T cell response in sepsis.

    Science.gov (United States)

    Yang, Xianghong; Hu, Bangchuan; Sun, Renhua; Chen, Jianghua

    2014-06-01

    The development of sepsis invovles the dysfunction of immunity due to an imbalance between the hyperimmune response and the immunoparalysis. Immune cells in both the innate and acquired immune system, including neutrophils, macrophages, dendritic cells, T cells and NK cells, are actively involved in the process. The interaction between immune cells, proinflammatory and anti-inflammatory cytokines contribute to the immunoparalysis in sepsis. Abnormal CD4+ and CD8+ T cell responses are major components of the deregulated acquired immune response in sepsis. Immune dysfunction of regulatory T cells (Tregs) contributes to the pathogensis of sepsis. Furthermore, IL-7 is essential for the replenishment and survival of T cells, which represents a promising target for immunotherapy of sepsis. In this review, we discusse the the immunoparalysis in the sepsis, with a focus on the deregulation of T cell response.

  8. Early-Onset Neonatal Sepsis

    Science.gov (United States)

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  9. Hospital Incidence and Mortality Rates of Sepsis.

    Science.gov (United States)

    Fleischmann, Carolin; Thomas-Rueddel, Daniel O; Hartmann, Michael; Hartog, Christiane S; Welte, Tobias; Heublein, Steffen; Dennler, Ulf; Reinhart, Konrad

    2016-03-11

    Sepsis, the most severe manifestation of acute infection, poses a major challenge to health care systems around the world. To date, adequate data on the incidence and mortality of sepsis in Germany have been lacking. Nationwide case-related hospital DRG statistics for the years 2007-2013 were used to determine the in-hospital incidence and mortality of sepsis. Cases were identified on the basis of the clinical and pathogen-based ICD-10 codes for sepsis. The statistical evaluation was standardized for age and sex and carried out separately for each age group. The number of cases of sepsis rose by an average of 5.7% per year, from 200 535 in 2007 to 279 530 in 2013, corresponding to an increase in the adjusted in-hospital incidence from 256 to 335 cases per 100 000 persons per year. The percentage of patients with severe sepsis rose from 27% to 41%. The in-hospital mortality of sepsis fell over the same period by 2.7%, to 24.3%. In 2013, 67 849 persons died of sepsis in German hospitals (or died of another disease, but also had sepsis). The incidence was highest in the youngest and oldest age groups, and the in-hospital mortality rose nearly linearly with age from age 40 onward. Sepsis and death from sepsis are markedly more common in Germany than previously assumed, and they are on the rise. Sepsis statistics should become a standard component of federal statistical reports on public health, as well as of hospital statistics. Preventive measures and evidencebased treatment should be implemented across the nation.

  10. Intraintestinal administration of ulinastatin protects against sepsis by relieving intestinal damage.

    Science.gov (United States)

    Yang, Bingchang; Gao, Min; Wang, Kangkai; Jiang, Yu; Peng, Yue; Zhang, Huali; Yang, Mingshi; Xiao, Xianzhong

    2017-05-01

    Intravenous administration of ulinastatin (UTI), a broad spectral protease inhibitor, has been used on an experimental basis with severe sepsis patients in Asia. However, the effects of intraintestinal administration of UTI on intestinal and multiple organ damage in sepsis have not been reported. In this study, we established a sepsis model in rats using cecal ligation and puncture and compared the effects of intraintestinal administration of UTI through an artificial fistula of duodenum and intraperitoneal administration of UTI on the pathophysiological changes of sepsis. It was found that intraintestinal administration of UTI (1) significantly improved the survival of septic rats, (2) significantly reduced the serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 as well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal microscopic and ultrastructural damage of septic rats. In addition, the protective effects of intraintestinal administration of UTI were significantly better than those of intraperitoneal administration of UTI. Overall, the present study for the first time revealed that intraintestinal administration of protease inhibitor UTI could reduce systemic inflammatory responses and multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of intestinal wall due to proteases and provided new research ideas and experimental evidences for treatment of sepsis by intraintestinal administration of UTI. Copyright © 2016. Published by Elsevier Inc.

  11. Current insights in sepsis: from pathogenesis to new treatment targets

    NARCIS (Netherlands)

    Wiersinga, W. Joost

    2011-01-01

    Sepsis continues to be a leading cause of ICU death. This review summarizes current knowledge on sepsis pathogenesis and new therapeutical strategies. Although systemic inflammatory response syndrome predominates in early sepsis, the compensatory anti-inflammatory response syndrome causes

  12. Sepsis management in the deployed field hospital.

    Science.gov (United States)

    Johnston, Andrew McD; Easby, D; Ewington, I

    2013-09-01

    Sepsis, a syndrome caused by severe infection, affects a small proportion of military casualties but has a significant effect in increasing morbidity and mortality, including causing some preventable deaths. Casualties with abdominal trauma and those with significant tissue loss appear to be at a greater risk of sepsis. In this article, the diagnosis and management of sepsis in military casualties with reference to the Surviving Sepsis Campaign guidelines are examined. We discuss the management considerations specific to military casualties in the deployed setting and also discuss factors affecting evacuation by the UK Royal Air Force Critical Care Air Support Team.

  13. ENDOGENOUS INTOxICATION AND SEPSIS

    Directory of Open Access Journals (Sweden)

    I. V. Aleksandrova

    2014-01-01

    Full Text Available RELEVANCE. Sepsis is always accompanied by endogenous intoxication (EI. It is very important to study EI in the patients with severe sepsis and septic shock.MATERIAL AND METHODS. Twenty seven patients with severe sepsis and thirteen with septic shock in the postoperative period were enrolled into the study. EI was assessed using the measurements of total and effective albumin concentrations (EAC, middle-molecular-weight proteins (MMWP and EI index (Kei=MMWP/ EACx1000.RESULTS. The use of the EI index in patients with severe sepsis and septic shock leads to improvement of diagnostic and therapy monitoring.

  14. Efek Probiotik terhadap Mortalitas, Derajat Inflamasi Intestinal, dan Kadar IgA pada Mencit Model Sepsis

    Directory of Open Access Journals (Sweden)

    Yoseph Indrayanto

    2013-03-01

    Full Text Available Sepsis results in changes to the microbiology of the gastrointestinal tract, leading to a loss of commensal flora and an overgrowth of potentially pathogenic bacteria. Administering probiotics to sepsis patients may restore balance to the microbiota and have positive effects on immune function and gastrointestinal structure and function. This study was aimed to evaluate the effect of probiotic on mortality, intestinal inflammation and immunoglobulin A (IgA serum level in mice model of sepsis. This study was an experimental research laboratory, with 36 male Balb/C mice were divided into: control, sepsis, and sepsis+probiotic groups. The study was conducted at Histology and Biomedical Laboratory, School of Medicine, Sebelas Maret University, Surakarta, in January to April 2012. Sepsis was induced in the male Balb/C mice using an intraperitoneally (i.p injection of cecal inoculum (200 mg/ kgBW, for sepsis mice model and sepsis with probiotic. Control mice were not inoculation during the study. Detection of intestinal inflammation with hematoxylin and eosin (HE staining on 8th day. Mortality perceived until 8th day. IgA serum level measurement with enzyme-linked immunosorbent assay. Two-tailed Fisher exact test for the analysis of mortality, Kruskal-Wallis test for the intestinal inflammation, one way analysis of variance for IgA serum level. Probiotic showed no significantly mortality (10% vs 40%, p=0.065 compared to sepsis group. Probiotic showed significantly decreased intestinal inflammation compared to sepsis group (p<0.001. Control mice showed levels of IgA 35.82±4.55 ng/mL. Probiotic showed significantly increased IgA levels (65.07±34.97 ng/mL vs 6.20±5.80 ng/mL, p<0.001 compared to sepsis group. In conclusions, probiotic decrease intestinal inflammation and mortality, on the other hand increase IgA level in mice model of sepsis.

  15. Survival benefits of remote ischemic conditioning in sepsis.

    Science.gov (United States)

    Joseph, Bellal; Khalil, Mazhar; Hashmi, Ammar; Hecker, Louise; Kulvatunyou, Narong; Tang, Andrew; Friese, Randall S; Rhee, Peter

    2017-06-01

    Sepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model. Eight to 12 week C57BL/6 mice received intra-peritoneal injection of 12.5-mg/kg lipopolysaccharide (LPS). Septic animals in the experimental group underwent RIC at 0, 2, and 6 h after LPS by surgical exploration and alternate clamping of the femoral artery. Six 4-min cycles of ischemia-reperfusion were performed. Primary outcome was survival at 5-d after LPS injection. Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection). Kaplan-Meier survival analysis and log-rank test were used. ANOVA test was used to compare cytokine measurements. We performed experiments on 44 mice: 14 sham and 30 RIC mice (10 at each time point). Overall survival was higher in the experimental group compared to the sham group (57% versus 21%; P = 0.02), with the highest survival rate observed in the 2-hour post-RIC group (70%). On Kaplan-Meier analysis, 2-h post-RIC group had increased survival at 5 days after LPS (P = 0.04) with hazard ratio of 0.3 (95% confidence interval = 0.09-0.98). In the RIC group, serum concentrations of IFN-γ, IL-10, IL-1β, and TNFα peaked at 2 h after LPS and then decreased significantly over 24 hours (P sepsis and has the potential for implementation in the clinical practice. Early implementation of RIC may play an

  16. Sepsis neonatal por Estreptococos Pyogenes Neonatal Sepsis by Streptococcus pyogenes

    OpenAIRE

    Gilberto Rodríguez-Herrera; Cinthya Ramírez-Navarro

    2009-01-01

    Se presenta el caso de un paciente masculino, recién nacido a término adecuado para la edad gestacional, quien nace por parto vaginal, con el antecedente de fiebre en la madre durante el periodo de postparto inmediato. Los padres consultan a los 2 días de vida pues le notan dificultad respiratoria, hipoactividad y rechazo a la leche materna. El paciente se interna y se aborda como una sepsis. Durante su estancia en el servicio de neonatología del Hospital Nacional de Niños asocia fallo respir...

  17. 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

  18. Methionine Metabolites in Patients With Sepsis.

    Science.gov (United States)

    Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

    2018-01-01

    Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

  19. Procalcitonin as an adjunctive biomarker in sepsis

    Directory of Open Access Journals (Sweden)

    Mahua Sinha

    2011-01-01

    Full Text Available Sepsis can sometimes be difficult to substantiate, and its distinction from non-infectious conditions in critically ill patients is often a challenge. Serum procalcitonin (PCT assay is one of the biomarkers of sepsis. The present study was aimed to assess the usefulness of PCT assay in critically ill patients with suspected sepsis. The study included 40 patients from the intensive care unit with suspected sepsis. Sepsis was confirmed clinically and/or by positive blood culture. Serum PCT was assayed semi-quantitatively by rapid immunochromatographic technique (within 2 hours of sample receipt. Among 40 critically ill patients, 21 had clinically confirmed sepsis. There were 12 patients with serum PCT ≥10 ng/ml (8, blood culture positive; 1, rickettsia; 2, post-antibiotic blood culture sterile; and 1, non-sepsis; 7 patients with PCT 2-10 ng/ml (4, blood culture positive; 1, falciparum malaria; 2, post-antibiotic blood culture sterile; 3 patients with PCT of 0.5 to 2 ng/ml (sepsis in 1 patient; and 18 patients with PCT < 0.5 ng/ml (sepsis in 2 patients. Patients with PCT ≥ 2 ng/ml had statistically significant correlation with the presence of sepsis (P<0.0001. The PCT assay revealed moderate sensitivity (86% and high specificity (95% at a cut-off ≥ 2 ng/ml. The PCT assay was found to be a useful biomarker of sepsis in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.

  20. Lactic acidosis, hyperlactatemia and sepsis

    Directory of Open Access Journals (Sweden)

    Andrea Montagnani

    2016-12-01

    Full Text Available Among hospitalized patients, lactic acidosis represents the most common cause of metabolic acidosis. Lactate is not just a metabolic product of anaerobic glycolysis but is triggered by a variety of metabolites even before the onset of anaerobic metabolism as part of an adaptive response to a hypermetabolic state. On the basis of such considerations, lactic acidosis is divided into two classes: inadequate tissue oxygenation (type A and absence of tissue hypoxia (type B. Lactic acidosis is characterized by non-specific symptoms but it should be suspected in all critical patients who show hypovolemic, hypoxic, in septic or cardiogenic shock or if in the presence of an unexplained high anion gap metabolic acidosis. Lactic acidosis in sepsis and septic shock has traditionally been explained as a result of tissue hypoxia when whole-body oxygen delivery fails to meet whole body oxygen requirements. In sepsis lactate levels correlate with increased mortality with a poor prognostic threshold of 4 mmol/L. In hemodynamically stable patients with sepsis, hyperlactatemia might be the result of impaired lactate clearance rather than overproduction. In critically ill patients the speed at which hyperlactatemia resolves with appropriate therapy may be considered a useful prognostic indicator. The measure of blood lactate should be performed within 3 h of presentation in acute care setting. The presence of lactic acidosis requires early identification of the primary cause of shock for the best appropriate treatment. Since most cases of lactic acidosis depend on whole-body oxygen delivery failure, the maximization of systemic oxygen delivery remains the primary therapeutic option. When initial resuscitation does not substantially or completely correct lactic acidosis, it is also essential to consider other causes. The treatment of acidosis with buffering agents (specifically bicarbonate is generally advocated only in the setting of severe acidosis. Ongoing

  1. Mechanisms of enhanced lung injury during sepsis

    DEFF Research Database (Denmark)

    Czermak, B J; Breckwoldt, M; Ravage, Z B

    1999-01-01

    A major complication in sepsis is progressively impaired lung function and susceptibility to intrapulmonary infection. Why sepsis predisposes the lung to injury is not clear. In the current studies, rats were rendered septic by cecal ligation/puncture and evaluated for increased susceptibility...

  2. Maternal sepsis: epidemiology, etiology and outcome.

    Science.gov (United States)

    van Dillen, Jeroen; Zwart, Joost; Schutte, Joke; van Roosmalen, Jos

    2010-06-01

    Sepsis is a major cause of maternal death worldwide. Little is known on the incidence of severe maternal morbidity related to sepsis. In this review, we focus on new findings concerning epidemiology, etiology and outcome of maternal sepsis in low-income as well as high-income countries. It is estimated that puerperal sepsis causes at least 75,000 maternal deaths every year, mostly in low-income countries. Studies from high-income countries report incidence of maternal morbidity due to sepsis of 0.1-0.6 per 1000 deliveries. The causative microorganisms are generally polymicrobial with beta-haemolytic streptococci group A (GAS) often being the cause of severe cases of puerperal fever. The single most important risk factor for postpartum infection seems to be caesarean section, and prophylactic antibiotics during the procedure substantially reduce the infection risk. Improvements in service provision as promoted through the Surviving Sepsis Campaign can reduce the overall risk of mortality and morbidity from maternal sepsis in high-income as well as in low-income countries. Maternal sepsis is an infrequent, but important complication of pregnancy, childbirth and puerperium, resulting in significant maternal morbidity and mortality worldwide. Improved outcome is possible through improved service provision.

  3. 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...

  4. Think Sepsis. Time Matters. PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2016-08-23

    This 60 second public service announcement is based on the August 2016 CDC Vital Signs report. Sepsis is a medical emergency and can happen quickly. Learn the signs of sepsis and how to prevent it.  Created: 8/23/2016 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 8/23/2016.

  5. Severe sepsis and septic shock [author's reply

    NARCIS (Netherlands)

    Angus, Derek C.; van der Poll, Tom

    2013-01-01

    To the Editor: We would like to address two potentially confusing issues concerning venous oxygen saturation (Svo(2)) as presented in Table 1 of the review by Angus and van der Poll (Aug. 29 issue).(1) First, Table 1 suggests that Svo(2) is raised in sepsis, severe sepsis, and septic shock.

  6. Vasopressin – Emerging Importance in Sepsis

    African Journals Online (AJOL)

    QuickSilver

    currently being used in CPR, Septic shock, Post CPB shock and in other areas requiring a vasopressor. Vasopressin and Sepsis. Vasopressin's use in sepsis stemmed originally from Landry's observation in 1994 that patients in vasodilatory septic shock were very sensitive to the vasopressor action of infused Vaso- pressin.

  7. Intrathecal baclofen withdrawal mimicking sepsis.

    Science.gov (United States)

    Kao, Louise W; Amin, Yama; Kirk, Mark A; Turner, Michael S

    2003-05-01

    Baclofen (Lioresal) is a drug of choice to treat spasticity and is increasingly being administered intrathecally via an implantable pump in cases refractory to oral therapy. Emergency physicians will likely treat patients with baclofen withdrawal or overdose as this treatment becomes more widespread. The syndrome of baclofen withdrawal presents with altered mental status, fever, tachycardia, hypertension or hypotension, seizures, and rebound spasticity, and may be fatal if not treated appropriately. Baclofen withdrawal may mimic other diseases including sepsis, meningitis, autonomic dysreflexia, malignant hyperthermia, or neuroleptic malignant syndrome. Treatment consists of supportive care, reinstitution of baclofen, benzodiazepines, and diagnosis and eventual repair of intrathecal pump and catheter malfunction.

  8. Sepsis neonatal por Estreptococos Pyogenes

    OpenAIRE

    Gilberto Rodríguez-Herrera; Cinthya Ramírez-Navarro

    2009-01-01

    Se presenta el caso de un paciente masculino, recién nacido a término adecuado para la edad gestacional, quien nace por parto vaginal, con el antecedente de fiebre en la madre durante el periodo de postparto inmediato. Los padres consultan a los 2 días de vida pues le notan dificultad respiratoria, hipoactividad y rechazo a la leche materna. El paciente se interna y se aborda como una sepsis. Durante su estancia en el servicio de neonatología del Hospital Nacional de Niños asocia fallo respir...

  9. The role of heparin in sepsis: much more than just an anticoagulant.

    Science.gov (United States)

    Li, Xu; Ma, Xiaochun

    2017-11-01

    Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

  10. Farnesoid X Receptor Regulation of the NLRP3 Inflammasome Underlies Cholestasis-Associated Sepsis.

    Science.gov (United States)

    Hao, Haiping; Cao, Lijuan; Jiang, Changtao; Che, Yuan; Zhang, Songyang; Takahashi, Shogo; Wang, Guangji; Gonzalez, Frank J

    2017-04-04

    Cholestasis is a common complication of sepsis, and the increased plasma levels of bile acids are predictive of sepsis-associated mortality. However, the exact mechanism by which cholestasis aggravates sepsis development remains elusive. Here, we show that bile acids are danger-associated molecular patterns (DAMPs) that can activate both signal 1 and 2 of the NLRP3 inflammasome in inflammatory macrophages. Mechanistically, bile acids induce a prolonged calcium influx and activate the NLRP3 inflammasome synergistically with ATP. Experimental cholestasis sensitizes, while cholestyramine, a bile acid sequestrant, protects mice from LPS-induced sepsis. FXR negatively regulates the NLRP3 inflammasome via physical interaction with NLRP3 and caspase 1. Fxr-null mice are more sensitive, while FXR-overexpressing mice are more resistant, to endoxemia shock. These findings suggest that bile acids and FXR play pivotal roles in sepsis via controlling the NLRP3 inflammasome, and that targeting FXR may represent a therapeutic strategy for cholestasis-associated sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    ABSTRACT: Sepsis is one of the leading causes of mortality in non-cardiac intensive care units, and the need for markers of progression and severity are high. Also, treatment of sepsis is highly debated and potential new targets of treatment are of great interest. In the previous issue of Critical...... Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...

  12. [Advances in immunotherapeutic research of sepsis].

    Science.gov (United States)

    Dong, Lihua; Lyu, Juan; Ding, Lili; Liu, Zhongmin

    2017-02-01

    Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Despite decades of research, it remains the leading cause of death in intensive care units (ICUs). None of the current treatment, including antibiotics, organ protection and liquid resuscitation, is specifically effective for sepsis. Immunosuppression is one of the currently accepted pathogenesis and immunotherapy is one of the hot spot of current sepsis research. Immune related treatments include restricting the release of pathogen toxin and its removal, controlling the excessive inflammatory reaction and apoptosis inhibition, etc. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7 (IL-7), anti-programmed cell death-1 (PD-1) antibody and others, have demonstrated reversal of T cell dysfunction and improved survival resulting from reviewing recent advances in immunotherapy of sepsis. Therefore, immunotherapy may be a new way of sepsis treatment.

  13. Impact of 6-Hour Sepsis Resuscitation Bundle Compliance on Hospital Mortality in a Saudi Hospital

    Directory of Open Access Journals (Sweden)

    Javed I. Memon

    2012-01-01

    Full Text Available Purpose. To assess the effect of improved compliance with 6-hour sepsis resuscitation bundle on mortality in patients with severe sepsis and septic shock. Materials and Methods. A quasi-experimental prospective study was conducted at a 10-bedded combined medical and surgical intensive care unit. The historical group included all consecutive patients with severe sepsis and septic shock admitted from January 2008 to March 2009. Intervention included evidence-based written sepsis pathway, antibiotic recommendations, and an educational program.The post-intervention group included all consecutive patients admitted from July 2009 to June 2011. The primary outcome measures were the overall compliance to seven 6-hour sepsis resuscitation bundle elements and 30-day hospital mortality. There were 99 patients in the historical group and 199 in the post-intervention group. Results. The baseline patients' characteristics were similar. Overall compliance to all seven sepsis resuscitation bundle elements in historical group was 5.1% [95% confidence interval (CI, 2.1–11.3] which improved after intervention to 23.6% (95% CI, 17.9–30.1; . The overall compliance to 6-hour sepsis resuscitation bundle elements was associated with improved survival [odds ratio (OR, 5.8 (95% CI, 2.2–15.1; ]. 30-day hospital mortality reduced from 31.3% in the historical group to 21.1% in the intervention group; . Conclusion. Improvement in compliance to 6-hour sepsis resuscitation bundle was associated with a reduction in 30-day hospital mortality.

  14. Sirtuin 2 Regulates Microvascular Inflammation during Sepsis

    Directory of Open Access Journals (Sweden)

    Nancy Buechler

    2017-01-01

    Full Text Available Objective. Sepsis and septic shock, the leading causes of death in noncoronary intensive care units, kill more than 200,000/year in the US alone. Circulating cell-endothelial cell interactions are the rate determining factor in sepsis inflammation. Sirtuin, a seven-member family of proteins (SIRT1–7, epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3, and 6 in sepsis previously. In this project, we studied the role of SIRT2 on sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT, SIRT2 knockout (SIRT2KO, and SIRT2 overexpressing (SIRT2KI mice by cecal ligation and puncture (CLP. We studied leukocyte/platelet adhesion using intravital microscopy and E-selectin/ICAM-1 adhesion molecule expression in the small intestine with immunohistochemistry (IHC six hours post-CLP/sham surgery. We also studied 7-day survival rates in WT, SIRT2KO, and SIRT2KI sepsis mice. Results. Compared to WT mice, SIRT2KO mice show exaggeration while SIRT2KI mice show attenuation of cellular adhesion with sepsis in the small intestine. We also show that the small intestinal E-selectin and ICAM-1 expressions increased in SIRT2KO and decreased in SIRT2KI mice versus those in WT sepsis mice. We show that the 7-day survival rate is decreased in SIRT2KO and increased in SIRT2KI sepsis mice. Conclusion. SIRT2 modulates microvascular inflammation in sepsis and affects survival.

  15. Disruption of Brain-Heart Coupling in Sepsis

    NARCIS (Netherlands)

    Admiraal, Marjolein M.; Gilmore, Emily J.; Van Putten, Michel J.A.M.; Zaveri, Hitten P.; Hirsch, Lawrence J.; Gaspard, Nicolas

    2017-01-01

    Purpose: To investigate heart rate and EEG variability and their coupling in patients with sepsis and determine their relationship to sepsis severity and severity of sepsis-Associated brain dysfunction. Methods: Fifty-Two patients with sepsis were prospectively identified, categorized as comatose (N

  16. Sepsis

    Science.gov (United States)

    ... medical treatments include: Oxygen to help with breathing Fluids given through a vein Medicines that increase blood pressure Dialysis if there is kidney failure A breathing machine ( mechanical ventilation ) if there is lung failure

  17. Sepsis

    Science.gov (United States)

    ... with weakened immune systems Infants and children The elderly People with chronic illnesses, such as diabetes, AIDS, cancer, and kidney or liver disease People suffering from a severe burn or physical ...

  18. Utility of cytokines to predict neonatal sepsis.

    Science.gov (United States)

    Ye, Qing; Du, Li-Zhong; Shao, Wen-Xia; Shang, Shi-Qiang

    2017-04-01

    Sepsis is an important cause of neonatal morbidity and mortality worldwide. Diagnosis and treatment of neonatal sepsis relies on clinical judgment and interpretation of nonspecific laboratory tests. In a prospective cohort, we measured inflammatory cytokines as a potential biomarker for neonatal sepsis. Serum inflammatory cytokine levels were evaluated in the early stage of neonatal sepsis and after antimicrobial treatment. Receiver operating characteristic curves assessed the diagnostic value of cytokines. We performed multiple logistic regression analysis to characterize the role of each cytokine independently for infants with culture proven sepsis. C-reactive protein, interleukin (IL)-6, IL-10 and IL-6/IL-10 levels were significantly elevated in neonatal sepsis when compared with the control group and there were 1.4 (95% confidence interval (CI): 1.2-1.5), 4.9 (95% CI: 4.6-5.1), 5.1 (95% CI: 4.5-5.6), and 10.2 (95% CI: 9.2-11.1) fold greater odds, respectively, to predict neonatal sepsis when increased. After effective treatment, median IL-6 (pretreatment value: 263.0 pg/ml and post-treatment value: 7.4 pg/ml) and IL-6/IL-10 levels (pretreatment value: 16.6 and post-treatment value: 1.4) significantly decreased. The areas under the curve for IL-6, IL-10, IL-6/IL-10 and C-reactive protein for differential diagnosis were 0.98, 0.82, 0.90, and 0.88, respectively. IL-6 and IL-6/IL-10 outperformed C-reactive protein to diagnose neonatal sepsis. Of the cytokines studied, IL-6 was the most sensitive, whereas IL-6/IL-10 was the most specific predictor of neonatal sepsis.

  19. Plasma arginine correlations in trauma and sepsis.

    Science.gov (United States)

    Chiarla, C; Giovannini, I; Siegel, J H

    2006-02-01

    Arginine (ARG) is an amino acid (AA) with unique properties and with a key-role in the metabolic, immune and reparative response to trauma and sepsis. This study has been performed to characterize the correlations between plasma levels of ARG, of other AA and of multiple metabolic variables in trauma and sepsis. Two-hundred and sixty-three plasma amino-acidograms with a large series of additional biochemical and blood variables were obtained consecutively in 9 trauma patients who developed sepsis, undergoing total parenteral nutrition with dextrose, fat and a mixed AA solution containing 10.4% arginine. ARG was low soon after trauma, then it increased with increasing distance from trauma and with the development of sepsis. ARG was also directly related to the AA infusion rate (AAIR) and for any given AAIR, was lower after trauma than after the development of sepsis. ARG was also related directly to the plasma levels of most of the other AA, the best correlation being that with lysine (r(2) = 0.81, p AAIR and urinary 3-methylhistidine excretion (accounting for the effect of endogenous proteolysis) (multiple r(2) = 0.70, p AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis. Correlations of ORN with other AA levels were poorer than those found for ARG, however ORN was directly related to white blood cell and platelet count, fibrinogen, transferrin, cholesterol and many AA clearances. These data show that changes in ARG in trauma and sepsis are correlated with changes in other AA and, within these correlations, reconfirm a tendency to lower ARG in trauma compared to sepsis. The strong correlation with lysine warrants a deeper assessment of the practical implications of interdependency between these two AA. The data also suggest that changes in plasma ORN in trauma and sepsis may reflect adequacy of AA substrate to support acute-phase and other synthetic processes.

  20. Improving Diagnosis of Sepsis After Burn Injury Using a Portable Sepsis Alert System

    Science.gov (United States)

    2015-10-01

    Early initiation of antibiotics within 1 hour of recognition of sepsis is the only factor associated with better survival. Diagnosis of sepsis after...invasive vital signs’ can detect sepsis earlier, leading to earlier initiation of antibiotics and improved morbidity and mortality. 15. SUBJECT TERMS...patient data. In identifying this alternative and installing it, our project was delayed by approximately 9 months. With this increased capability to

  1. Epigenetic changes during sepsis: on your marks!

    Science.gov (United States)

    Bataille, Aurélien; Galichon, Pierre; Ziliotis, Marie-Julia; Sadia, Iman; Hertig, Alexandre

    2015-10-15

    Epigenetics is the study of how cells, organs, and even individuals utilize their genes over specific periods of time, and under specific environmental constraints. Very importantly, epigenetics is now expanding into the field of medicine and hence should provide new information for the development of drugs. Bomsztyk and colleagues have detected major epigenetic changes occurring in several organs as early as 6 h after the onset of a mouse model of multiple organ dysfunction syndrome induced by Staphylococcus aureus lung injury. Decrease in mRNA of key genes involved in endothelial function was found to be associated with (and potentially explained by) a decrease in permissive histone marks, while repressive marks were unchanged. We discuss here the limitations of a whole-organ as opposed to a cell-specific approach, the nature of the controls that were chosen, and the pitfalls of histone modifications as a cause of the eventual phenotype. While the use of 'epidrugs' is definitely welcome in the clinic, how and when they will be used in sepsis-related multiple organ dysfunction will require further experimental studies.

  2. Ensemble models of neutrophil trafficking in severe sepsis.

    Directory of Open Access Journals (Sweden)

    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

  3. Thromboelastography in patients with severe sepsis

    DEFF Research Database (Denmark)

    Haase, Nicolai; Ostrowski, Sisse Rye; Wetterslev, Jørn

    2015-01-01

    PURPOSE: To investigate the association between consecutively measured thromboelastographic (TEG) tracings and outcome in patients with severe sepsis. METHODS: Multicentre prospective observational study in a subgroup of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial (NCT00962156......) comparing hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate for fluid resuscitation in severe sepsis. TEG (standard and functional fibrinogen) was measured consecutively for 5 days, and clinical data including bleeding and death was retrieved from the trial database. Statistical analyses included Cox...... bleeding [HR 2.43 (1.16-5.07)] and possibly explained the excess bleeding with HES in the 6S trial. CONCLUSIONS: In our cohort of patients with severe sepsis, progressive hypocoagulability defined by TEG variables was associated with increased risk of death and increased risk of bleeding....

  4. The microcirculation is the motor of sepsis

    NARCIS (Netherlands)

    Ince, Can

    2005-01-01

    Regional tissue distress caused by microcirculatory dysfunction and mitochondrial depression underlies the condition in sepsis and shock where, despite correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction deficit persist. We have termed this condition

  5. Low bilirubin kernicterus with sepsis and hypoalbuminaemia.

    Science.gov (United States)

    Odutolu, Yetunde; Emmerson, Anthony J

    2013-04-23

    A near-term female neonate with total serum bilirubin levels not exceeding the exchange transfusion level with hypoalbuminaemia developed abnormal movements while recovering from sepsis. Investigations showed an evidence of kernicterus on brain imaging and bilateral auditory neuropathic changes.

  6. Cardiorenal syndrome in sepsis: A narrative review.

    Science.gov (United States)

    Kotecha, Aditya; Vallabhajosyula, Saraschandra; Coville, Hongchuan H; Kashani, Kianoush

    2017-09-01

    Multi-organ dysfunction is seen in nearly 40-60% of all patients presenting with sepsis, including renal and cardiac dysfunction. Cardiorenal syndrome type-5 reflects concomitant cardiac and renal dysfunction secondary to a systemic condition that primarily affects both organs, such as sepsis. There are limited data on the etiology, pathogenesis and clinical implications of cardiorenal syndrome in sepsis. Cardiac dysfunction and injury can be measured with cardiac biomarkers, echocardiographic dysfunction, and hemodynamic parameters. Acute kidney injury is systematically evaluated using serum creatinine and urine output criteria. This review seeks to systematically describe the epidemiology, risk factors, pathogenesis, diagnosis and management of cardiorenal syndrome type-5 in the setting of sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Genetic polymorphisms and sepsis in premature neonates.

    Directory of Open Access Journals (Sweden)

    Susanna Esposito

    Full Text Available Identifying single nucleotide polymorphisms (SNPs in the genes involved in sepsis may help to clarify the pathophysiology of neonatal sepsis. The aim of this study was to evaluate the relationships between sepsis in pre-term neonates and genes potentially involved in the response to invasion by infectious agents. The study involved 101 pre-term neonates born between June 2008 and May 2012 with a diagnosis of microbiologically confirmed sepsis, 98 pre-term neonates with clinical sepsis and 100 randomly selected, otherwise healthy pre-term neonates born during the study period. During the study, 47 SNPs in 18 candidate genes were genotyped on Guthrie cards using an ABI PRISM 7900 HT Fast real-time and MAssARRAY for nucleic acids instruments. Genotypes CT and TT of rs1143643 (the IL1β gene and genotype GG of rs2664349GG (the MMP-16 gene were associated with a significantly increased overall risk of developing sepsis (p = 0.03, p = 0.05 and p = 0.03, whereas genotypes AG of rs4358188 (the BPI gene and CT of rs1799946 (the DEFβ1 gene were associated with a significantly reduced risk of developing sepsis (p = 0.05 for both. Among the patients with bacteriologically confirmed sepsis, only genotype GG of rs2664349 (the MMP-16 gene showed a significant association with an increased risk (p = 0.02. Genotypes GG of rs2569190 (the CD14 gene and AT of rs4073 (the IL8 gene were associated with a significantly increased risk of developing severe sepsis (p = 0.05 and p = 0.01. Genotype AG of rs1800629 (the LTA gene and genotypes CC and CT of rs1341023 (the BPI gene were associated with a significantly increased risk of developing Gram-negative sepsis (p = 0.04, p = 0.04 and p = 0.03. These results show that genetic variability seems to play a role in sepsis in pre-term neonates by influencing susceptibility to and the severity of the disease, as well as the risk of having disease due to specific pathogens.

  8. Toll-like receptors in neonatal sepsis.

    LENUS (Irish Health Repository)

    O'Hare, Fiona M

    2013-06-01

    Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

  9. Neonatal infectious diseases: evaluation of neonatal sepsis.

    Science.gov (United States)

    Camacho-Gonzalez, Andres; Spearman, Paul W; Stoll, Barbara J

    2013-04-01

    Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal, and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation, and early initiation of therapy are required to prevent adverse outcomes. This article reviews recent trends in epidemiology and provides an update on risk factors, diagnostic methods, and management of neonatal sepsis. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent.

    Science.gov (United States)

    Maddens, Bert; Vandendriessche, Benjamin; Demon, Dieter; Vanholder, Raymond; Chiers, Koen; Cauwels, Anje; Meyer, Evelyne

    2012-09-01

    Despite extensive research, the mortality rate of patients with sepsis-induced acute kidney injury (AKI) is unacceptably high, especially in the elderly. Current sepsis models have difficulties in reproducing AKI. This study aimed to develop a novel, clinically relevant mouse model for sepsis-induced AKI by uterine ligation and inoculation of bacteria. In addition, the age dependency of the severity of sepsis and sepsis-induced AKI was studied by validating this model in three different age categories. Experimental animal investigation. University research laboratory. Young (12-14 wks), aged (46-48 wks), and old (70-72 wks) C57BL/6 female mice were used as models for adolescent, adult premenopausal, and elderly postmenopausal women, respectively. Uterine ligation and inoculation with 10 colony forming unit Escherichia coli or saline (sham) was performed; in vivo imaging with a luminescent Escherichia coli strain documented the course of infection. All mice had established Escherichia coli sepsis at 48 hrs postinfection, with higher mortality rate in old (43%) compared to aged (23%) or young (9%) mice. Infected mice had elevated serum or plasma cytokine, chemokine (tumor necrosis factor, interleukin-6, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and interleukin-10), and NOx concentrations compared to sham mice. AKI was confirmed by renal histology. Serum creatinine concentrations at 48 hrs increased with age (mean ± SEM; controls 0.18 ± 0.03 mg/dL, young 0.28 ± 0.03 mg/dL, aged 0.38 ± 0.05 mg/dL, and old 0.44 ± 0.06 mg/dL). The uterine ligation and inoculation model for sepsis-induced AKI starts from a real infectious focus and shows an age-dependent severity of septic AKI that resembles AKI in humans.

  11. Correlation between Protection against Sepsis by Probiotic Therapy and Stimulation of a Novel Bacterial Phylotype

    NARCIS (Netherlands)

    Gerritsen, J.; Timmerman, H.M.; Fuentes, S.; Minnen, L.P. van; Panneman, H.; Konstantinov, S.R.; Rombouts, F.M.; Gooszen, H.G.; Akkermans, L.M.; Smidt, H.; Rijkers, G.T.

    2011-01-01

    Prophylactic probiotic therapy has shown beneficial effects in an experimental rat model for acute pancreatitis on the health status of the animals. Mechanisms by which probiotic therapy interferes with severity of acute pancreatitis and associated sepsis, however, are poorly understood. The aims of

  12. Correlation between protection against sepsis by probiotic therapy and stimulation of a novel bacterial phylotype

    NARCIS (Netherlands)

    Gerritsen, J.; Timmerman, H.M.; Fuentes, S.; Minnen, van L.P.; Panneman, H.; Konstantinov, S.R.; Rombouts, F.M.; Gooszen, H.G.; Akkermans, L.M.A.; Smidt, H.; Rijkers, G.T.

    2011-01-01

    Prophylactic probiotic therapy has shown beneficial effects in an experimental rat model for acute pancreatitis on the health status of the animals. Mechanisms by which probiotic therapy interferes with severity of acute pancreatitis and associated sepsis, however, are poorly understood. The aims of

  13. ADIPONECTIN DIMINISHES ORGAN-SPECIFIC MICROVASCULAR ENDOTHELIAL CELL ACTIVATION ASSOCIATED WITH SEPSIS

    NARCIS (Netherlands)

    van Meurs, Matijs; Castro, Pedro; Shapiro, Nathan I.; Lu, Shulin; Yano, Midori; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Ichiro; Zijlstra, Jan G.; Molema, Grietje; Parikh, Samir M.; Aird, William C.; Yano, Kiichiro

    Experimental sepsis was induced in male C57BL/6j, adiponectin-deficient mice (ADPNKO), and wild-type littermates by i.p. injection of 16 mg/kg lipopolysaccharide or cecal ligation and puncture. Blood and tissue samples were harvested 24 h after model induction. Circulating adiponectin is reduced in

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

    Directory of Open Access Journals (Sweden)

    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

  15. Aspectos histomorfológicos e respiratórios em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina Histomorphologic and respiratory aspects of acute lung injury in rats induced by experimental sepsis and under pentoxifylline treatment

    Directory of Open Access Journals (Sweden)

    Wagner Rogerio Souza de Oliveira

    2009-01-01

    Full Text Available OBJETIVO: Analisar as alterações histomorfológicas e respiratórias em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina. MÉTODOS: Foram utilizados 15 ratos adultos distribuídos em três grupos (n=5, por grupo, assim constituídos: GC - receberam apenas ventilação mecânica; GS - Animais sépticos tratados com solução salina e mecanicamente ventilados; GS+PTX - Animais sépticos, com infusão de pentoxifilina e mecanicamente ventilados. Todos os animais foram ventilados por um período de 180 minutos. Ao final deste período, foram avaliadas variáveis gasométricas (gasometria arterial, gravimétricas (relação peso úmido/peso seco, concentração de proteínas totais no lavado broncoalveolar e histomorfométricas (espessura dos septos alveolares. Os dados obtidos foram submetidos a análise estatística (P OBJECTIVE: Respiratory repercussion on acute lung injury in a model of induced sepsis intraperitoneally. METHODS: Fifteen animals taken at random were submitted to adult male Wistar rats. The rats were randomly divided into 3 groups (n=15: Group C - control group received only mechanical ventilation; Group S - rats received live Escherichia coli (E. coli intraperitoneally (septic and after 6 hours they were treated with normal saline infusion and ventilated with a low tidal volume. Group S+PTX - rats received live Escherichia coli intraperitoneally (septic and after 6 hours they were treated with pentoxifylline (PTX infusion and ventilated with a low tidal volume. All animals were ventilated during 180 minutes. We analyzed the arterial blood gases, gravimetric indices and histomorphometric analysis. RESULTS: Blood gases, wet to dry ratios, and total protein concentrations in the bronchoalveolar lavage were analyzed in all experimental groups. In the end of the experiment the partial pressure of oxygen was higher in the GS+PTX (460,0 ± 38,2 mmHg compared with GS (336,0 ± 14,6 mmHg. Pentoxifylline with

  16. Prediction about severity and outcome of sepsis by proatrial

    Directory of Open Access Journals (Sweden)

    WANG Rui-lan

    2010-06-01

    Full Text Available Sepsis is one of the most frequent causes of death in intensive care unit (ICU patients worldwide. According to recent reports, the incidence of sepsis has been rising at a rate of 1.5%-8% per year.1 About 9% of the sepsis develops to serious sepsis and 3% to septic shock. Although great progress has been made in the treatment of sepsis, themortality of patients with severe sepsis is still as high as 30%- 70%.2-4 Moreover, the high expenditure of sepsis management has resulted in a heavy financial burden to the government and patients.1 Therefore, howto estimatethe severity of sepsis early and apply targeted therapies timely is very important in the treatment of sepsis.

  17. 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...... endotoxin. 40 min later, half of the pigs were treated with plasmapheresis which lasted 4 h. The adhesion molecules, the oxidative burst, the number of neutrophils in blood and lungs, and cytokines were measured. RESULTS: Infusion of endotoxin was associated with activation of adhesion molecules increased...... infusion, it only temporarily attenuated a part of the activated cell-mediated immunity....

  18. Disassociation of Static and Dynamic Cerebral Autoregulatory Performance in Healthy Volunteers After Lipopolysaccharide Infusion and in Patients with Sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan Martin Griffin; Plovsing, Ronni R.; Ronit, Andreas

    2012-01-01

    -experimental model of the systemic inflammatory response during early sepsis, and (ii) in patients with advanced clinical sepsis. Cerebral autoregulation was tested using transcranial Doppler ultrasonography (i) before and after lipopolysaccharide (LPS) infusion in healthy volunteers (n=9), and (ii) in patients...... with sepsis (n=16). Static autoregulation was tested by norepinephrine infusion and dynamic autoregulation by transfer function analysis (TFA) of spontaneous oscillations between mean arterial blood pressure and middle cerebral artery blood flow velocity in the low frequency range (0.07-0.20 Hz). Static...... autoregulatory performance after LPS infusion and in patients with sepsis was similar to values in healthy volunteers at baseline. In contrast, TFA showed decreased gain and an increased phase difference between blood pressure and cerebral artery blood flow velocity after LPS (both p

  19. No agreement of mixed venous and central venous saturation in sepsis, independent of sepsis origin

    NARCIS (Netherlands)

    van Beest, Paul A.; van Ingen, Jan; Boerma, E. Christiaan; Holman, Nicole D.; Groen, Henk; Koopmans, Matty; Spronk, Peter E.; Kuiper, Michael A.

    2010-01-01

    Controversy remains regarding the relationship between central venous saturation (ScvO(2)) and mixed venous saturation (SvO(2)) and their use and interchangeability in patients with sepsis or septic shock. We tested the hypothesis that ScvO(2) does not reliably predict SvO(2) in sepsis. Additionally

  20. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee

  1. 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.

  2. Apelin attenuates postburn sepsis via a phosphatidylinositol 3-kinase/protein kinase B dependent mechanism: A randomized animal study.

    Science.gov (United States)

    Luo, Keqin; Long, Huibao; Xu, Bincan; Luo, Yanling

    2015-09-01

    This study aims to investigate whether apelin would regulate inflammatory response and promote survival in an experimental burn sepsis model through a phosphatidylinositol 3-kinase/protein kinase B dependent pathway. Male BALB/c mice were divided into the following groups: sham, burn, burn sepsis, burn sepsis treated with apelin, burn sepsis treated with apelin plus LY294002, and burn sepsis treated with LY294002 alone. Apelin level and inflammatory cytokines in serum were detected by enzyme-linked immuno sorbent assay. Apelin/APJ (apelin receptor, gene symbol APLNR) mRNA expression in spleen and adhesion molecules levels in lung was detected by real-time polymerase chain reaction. Neutrophil infiltration in lung was determined by myeloperoxidase assay. Phosphorylation of protein kinase B in lung was determined by western blot. Mortality rate was monitored. Burn sepsis induced decreased apelin/APJ mRNA expression in spleen and reduced apelin level in plasma, which were both restored by exogenous apelin treatment. Burn sepsis treated with apelin resulted in decreased interleukin-6, tumor-necrosis factor-alpha, interleukin -1β and monocyte chemotactic protein-1 levels in plasma. Mice with apelin treatment also showed decreased neutrophil infiltration and adhesion molecules expression, accompanied by a remarkable increased protein kinase B phosphorylation in lung tissue. The mortality rate in apelin treated animals was also significantly reduced. Importantly, the above effects of apelin were abolished by LY294002 treatment. Apelin regulates inflammatory response, diminishes inflammatory remote organ damage and improves survival in an experimental model of burn sepsis, which is at least partly mediated by a phosphatidylinositol 3-kinase/protein kinase B dependent pathway. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  3. Designing a Pediatric Severe Sepsis Screening Tool

    Directory of Open Access Journals (Sweden)

    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.

  4. Chronic medical conditions and risk of sepsis.

    Directory of Open Access Journals (Sweden)

    Henry E Wang

    Full Text Available We sought to determine the associations between baseline chronic medical conditions and future risk of sepsis.Longitudinal cohort study using the 30,239 community-dwelling participants of the REGARDS cohort. We determined associations between baseline chronic medical conditions and incident sepsis episodes, defined as hospitalization for an infection with the presence of infection plus two or more systemic inflammatory response syndrome criteria.Over the mean observation time of 4.6 years (February 5, 2003 through October 14, 2011, there were 975 incident cases of sepsis. Incident sepsis episodes were associated with older age (p<0.001, white race (HR 1.39; 95% CI: 1.22-1.59, lower education (p<0.001 and income (p<0.001, tobacco use (p<0.001, and alcohol use (p = 0.02. Incident sepsis episodes were associated with baseline chronic lung disease (adjusted HR 2.43; 95% CI: 2.05-2.86, peripheral artery disease (2.16; 1.58-2.95, chronic kidney disease (1.99; 1.73-2.29, myocardial infarction 1.79 (1.49-2.15, diabetes 1.78 (1.53-2.07, stroke 1.67 (1.34-2.07, deep vein thrombosis 1.63 (1.29-2.06, coronary artery disease 1.61 (1.38-1.87, hypertension 1.49 (1.29-1.74, atrial fibrillation 1.48 (1.21-1.81 and dyslipidemia 1.16 (1.01-1.34. Sepsis risk increased with the number of chronic medical conditions (p<0.001.Individuals with chronic medical conditions are at increased risk of future sepsis events.

  5. Elevated serum levels of lipoprotein‑associated phospholipase A2 predict mortality rates in patients with sepsis.

    Science.gov (United States)

    Huang, Zhongwei; Jiang, Haiyan; Cui, Xiaohui; Liang, Guiwen; Chen, Yu; Wang, Ting; Sun, Zhichao; Qi, Lei

    2018-01-01

    Sepsis remains one of the leading contributors to mortality rates in the intensive care unit (ICU) and emergency intensive care unit (EICU). Therefore, any treatments against the agents which produce sepsis in a medical emergency, are welcome. Elevated serum levels of lipoprotein‑associated phospholipase A2 (Lp‑PLA2) have been reported in a small cohort of patients with inflammation. The present study evaluated serum levels of Lp‑PLA2 in patients with sepsis and investigated the role of Lp‑PLA2 in sepsis. The investigation involved the selection of 151 patients with sepsis admitted to the emergency department of the Affiliated Hospital of Nantong University (Nantong, China) and 30 healthy controls. All patients (39 with sepsis, 55 with severe sepsis and 57 with septic shock) were examined on admission to the EICU. A complete blood count was performed, and serum levels of Lp‑PLA2, C‑reactive protein, procalcitonin, and interleukin 6, sequential organ failure (SOFA) scores and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were determined on hospital admission. The EICU and overall mortality rates were evaluated at baseline. The present study also assessed various laboratory parameters, clinical data and inflammatory cytokines. The patient follow up duration was 90 days. The data suggested that the serum levels of Lp‑PLA2 on admission to the EICU in patients with sepsis were elevated, compared with those in healthy controls. The concentrations of Lp‑PLA2 were correlated with the severity of disease, and were significantly associated with experimental markers of inflammation and established prognostic scores. In the total cohort, persistently elevated levels of Lp‑PLA2 on admission for EICU treatment was a predictor of poor prognosis, and provided superior diagnostic use, compared with the prognostic scoring systems, including SOFA or APACHE II scores. Taken together, the results suggested that Lp‑PLA2, with respect to other

  6. Global DNA methylation in neonatal sepsis.

    Science.gov (United States)

    Dhas, Benet Bosco; Antony, Hiasindh Ashmi; Bhat, Vishnu; Newton, Banupriya; Parija, Subhash Chandra

    2015-04-01

    To find out whether gDNA methylation can be used as a diagnostic/prognostic method for neonatal sepsis. The study was conducted in the neonatal division of a tertiary care referral hospital. Fifty one newborns as cases and thirty seven newborns as controls were enrolled in the study. Using 5-mC DNA ELISA method, the percentage of genomic DNA methylated in these newborns was established. Highly significant difference in percentage of gDNA methylated was found between the cases and controls (Cases: 2.4 ± 0.39; 2.07 ± 0.35; P sepsis (clinical, probable and culture positive) and without sepsis. Although the global DNA methylation was not a highly sensitive diagnostic method, this study reveals that DNA methylation might play a vital role in neonatal sepsis susceptibility. Identification of the specific differentially methylated genes might serve as a promising future diagnostic/prognostic marker for neonatal sepsis.

  7. Antimicrobial Sensitivity of Neonatal Bacterial Sepsis

    Directory of Open Access Journals (Sweden)

    Nadya Iswandari

    2017-06-01

    Full Text Available Background: Appropriate treatment on neonatal bacterial sepsis is important based on the exact etiology to prevent bacterial resistance, but bacterial identification using blood cultures requires a considerable time. The newest data of various bacteria and their sensitivity can be used to assist empirical antibiotics usage. This study was conducted to identify bacterial profile that caused neonatal sepsis and their sensitivity to antibiotics at Dr. Hasan Sadikin General Hospital Bandung.. Methods: A total of 275 neonatal sepsis cases and 288 blood cultures results were collected from a database provided by Dr. Hasan Sadikin General Hospital Bandung during the period of July 2011 toDecember 2012 (three semesters.  Etiology of the bacteria and antimicrobial sensitivity profile data were taken from positive bacteria results. Then, these variables were processed using the descriptive method and classified by semester Result: The most common bacteria that caused neonatal sepsis in the second semester 2011 is Serratia marescens, the first semester 2012 was Enterobacter aerogenes and in the second semester 2012 was Burkholderia cepacia. The most sensitive antibiotics were piperacillin tazobactam, cefepime, meropenem and amikacin in all three semesters, gentamycin in the second semester 2011 and 2012, and amoxicillin clavulanic in the second semester 2012. Conclusions: Bacterial and antimicrobial sensitivity profile is varied in every semester. Keywords: Antimicrobial sensitivity profile, bacterial profile, neonatal sepsis DOI: 10.15850/amj.v4n2.1072

  8. Comparison of Procalcitonin and C-reactive Protein in Differential Diagnosis of Sepsis and Severe Sepsis in Emergency Department

    Directory of Open Access Journals (Sweden)

    Ali Kemal Erenler

    2017-06-01

    Full Text Available Objective: Sepsis and severe sepsis (sepsis accompanied by acute organ dysfunction are leading causes of death worldwide. In this study, our aim was to investigate utility of biomarkers commonly used in diagnosis of sepsis in discriminating these two entities. Methods: Two-hundred and three patients involved were divided into 2 subgroups as sepsis and severe sepsis according to Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Then groups were compared according to clinical and laboratory (including C-reactive protein (CRP and procalcitonin (PCT levels characteristics. Results: Of 203 patients included into the study, 124 (61.1% were male and 79 (38.9% were female. The most common reason for sepsis was urinary tract infection (n=64, 31.5%, followed by catheter infection (n=16, 7.9% and pneumonia (n=14, 6.9%. Escherichia coli was the most common agent in both blood and urinary cultures. Majority of the patients were treated with ceftriaxone (n=33, 16.3%, followed by meronem/dapson (n=25, 12.3%. In both groups, CRP and PCT levels were high, even higher in severe sepsis group. However, any statistical significance could not be determined between groups. Mortality rate in sepsis patients was 6.4%. Conclusion: Plasma levels of both markers elevate in sepsis and severe sepsis. It was determined that CRP and PCT is higher in severe sepsis than in sepsis. However, the difference is not statistically significant. Plasma levels of CRP and PCT are not useful in differential diagnosis of sepsis and severe sepsis.

  9. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis.......To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis....

  10. The new sepsis definition: limitations and contribution to research and diagnosis of sepsis.

    Science.gov (United States)

    Verdonk, Franck; Blet, Alice; Mebazaa, Alexandre

    2017-04-01

    Based on recent clinical, epidemiological, and pathophysiological data, a third international consensus conference was carried out to define new criteria of sepsis in February 2016. This review presents the different items of this new definition, their limitations and their contribution to research and diagnosis of sepsis, in comparison with the previous definitions. Incidence, management, and pathophysiological knowledge of sepsis have improved over the past 20 years. However, sepsis still evolves to a mortal outcome, in one case out of five, with no new recent or specific therapy showing its efficacy on the patient's prognosis. These findings have led to the development of new definition. The new definition of sepsis incorporates relevant clinical and biological criteria such as SOFA score or serum lactate levels. It no longer takes into account the items of the systemic inflammatory response syndrome, which present a lack of specificity. It also simplifies the different stages of severity by deleting the term of 'severe sepsis' and by defining septic shock as a subset of sepsis. This definition, endorsed by only two international societies of intensive care, has some limitations and so merits prospective validation at different levels.

  11. Automated electronic medical record sepsis detection in the Emergency Department

    OpenAIRE

    Nguyen, Su; Mwakalindile, Edwin; Booth, James S.; Hogan, Vicki; Morgan, Jordan; Prickett, Charles T; Donnelly, John P.; Wang, Henry E.

    2014-01-01

    Background: While often first treated in the Emergency Department (ED), identification of sepsis is difficult. Electronic medical record (EMR) clinical decision tools offer a novel strategy for identifying patients with sepsis. The objective of this study was to test the accuracy of an EMR-based, automated sepsis identification system. Methods : We tested an EMR-based sepsis identification tool at a major academic, urban ED with 64,000 annual visits. The EMR system collected vital sign and la...

  12. Automated electronic medical record sepsis detection in the emergency department

    OpenAIRE

    Nguyen, Su Q.; Edwin Mwakalindile; Booth, James S.; Vicki Hogan; Jordan Morgan; Prickett, Charles T; Donnelly, John P.; Wang, Henry E.

    2014-01-01

    Background. While often first treated in the emergency department (ED), identification of sepsis is difficult. Electronic medical record (EMR) clinical decision tools offer a novel strategy for identifying patients with sepsis. The objective of this study was to test the accuracy of an EMR-based, automated sepsis identification system. Methods. We tested an EMR-based sepsis identification tool at a major academic, urban ED with 64,000 annual visits. The EMR system collected vital sign and lab...

  13. Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency.

    Science.gov (United States)

    Terashima, Asuka; Okamoto, Kazuo; Nakashima, Tomoki; Akira, Shizuo; Ikuta, Koichi; Takayanagi, Hiroshi

    2016-06-21

    Sepsis is a host inflammatory response to severe infection associated with high mortality that is caused by lymphopenia-associated immunodeficiency. However, it is unknown how lymphopenia persists after the accelerated lymphocyte apoptosis subsides. Here we show that sepsis rapidly ablated osteoblasts, which reduced the number of common lymphoid progenitors (CLPs). Osteoblast ablation or inducible deletion of interleukin-7 (IL-7) in osteoblasts recapitulated the lymphopenic phenotype together with a lower CLP number without affecting hematopoietic stem cells (HSCs). Pharmacological activation of osteoblasts improved sepsis-induced lymphopenia. This study demonstrates a reciprocal interaction between the immune and bone systems, in which acute inflammation induces a defect in bone cells resulting in lymphopenia-associated immunodeficiency, indicating that bone cells comprise a therapeutic target in certain life-threatening immune reactions. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Immunotherapy in the management of sepsis.

    Science.gov (United States)

    Sikora, Janusz Piotr

    2002-01-01

    This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.

  15. Implementation of an Inpatient Pediatric Sepsis Identification Pathway.

    Science.gov (United States)

    Bradshaw, Chanda; Goodman, Ilyssa; Rosenberg, Rebecca; Bandera, Christopher; Fierman, Arthur; Rudy, Bret

    2016-03-01

    Early identification and treatment of severe sepsis and septic shock improves outcomes. We sought to identify and evaluate children with possible sepsis on a pediatric medical/surgical unit through successful implementation of a sepsis identification pathway. The sepsis identification pathway, a vital sign screen and subsequent physician evaluation, was implemented in October 2013. Quality improvement interventions were used to improve physician and nursing adherence with the pathway. We reviewed charts of patients with positive screens on a monthly basis to assess for nursing recognition/physician notification, physician evaluation for sepsis, and subsequent physician diagnosis of sepsis and severe sepsis/septic shock. Adherence data were analyzed on a run chart and statistical process control p-chart. Nursing and physician pathway adherence of >80% was achieved over a 6-month period and sustained for the following 6 months. The direction of improvements met standard criteria for special causes. Over a 1-year period, there were 963 admissions to the unit. Positive screens occurred in 161 (16.7%) of these admissions and 38 (23.5%) of these had a physician diagnosis of sepsis, severe sepsis, or septic shock. One patient with neutropenia and septic shock had a negative sepsis screen due to lack of initial fever. Using quality improvement methodology, we successfully implemented a sepsis identification pathway on our pediatric unit. The pathway provided a standardized process to identify and evaluate children with possible sepsis requiring timely evaluation and treatment. Copyright © 2016 by the American Academy of Pediatrics.

  16. Effect of severe sepsis on platelet count and their indices

    African Journals Online (AJOL)

    EB

    Abstract. Background: Sepsis is a major disease affecting almost all organs and systems. Objectives: To examine platelet count and indices (mean platelet volume (MPV) and platelet distribution width (PDW)) in severe sepsis. Methods: Patients with criteria for sepsis at a first examination by an Infectious Diseases specialist ...

  17. Sepsis in HIV-infected patients; epidemiology and host response

    NARCIS (Netherlands)

    Huson, M.A.M.

    2016-01-01

    In this thesis, we examined the impact of HIV infection on the epidemiology (Part I) of sepsis, and host response (Part II) to sepsis. We studied sepsis patients in Gabon, a setting with a high prevalence of HIV, and in Dutch intensive care units (ICUs). In Part I, we found that HIV positive

  18. Implementatie van de Surviving Sepsis Campaign bundels : Monitoring van ervaringen

    NARCIS (Netherlands)

    Lilian Vloet; J. Schouten; N. Stevens; A. Rensen; A. Willems; F. Zeegers

    2011-01-01

    Sepsis komt vaak voor in ziekenhuizen. Ernstige sepsis is verantwoordelijk voor 10 - 20% van alle Intensive Care (IC) opnames en is de belangrijkste doodsoorzaak op niet-cardiale IC?s. De gemiddelde mortaliteit van volwassenen met ernstige sepsis op de IC is 33% en van volwassenen met septische

  19. Severe hyperglycaemia due to neonatal sepsis - A case report ...

    African Journals Online (AJOL)

    Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without accompanying bacteremia in the first month of life. The clinical signs of neonatal sepsis are neither specific nor uniform. Neonatal sepsis may present with fever, hypotonia, respiratory distress, apnea and hyperglycaemia.

  20. 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

  1. Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors

    NARCIS (Netherlands)

    Ree, Isabelle M. C.; Fustolo-Gunnink, Suzanne F.; Bekker, Vincent; Fijnvandraat, Karin J.; Steggerda, Sylke J.; Lopriore, Enrico

    2017-01-01

    Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. A cohort study was carried out among all

  2. Neonatal Sepsis: past, present and future; a review article | Tripathi ...

    African Journals Online (AJOL)

    Sepsis is the most common cause of neonatal mortality. As per National Neonatal Perinatal Database (NNPD) 2002-2003, the incidence of neonatal sepsis in India was 30 per 1000 live birth. It is 3% among intramural babies and 39.7% among extramural admissions. The early manifestations of neonatal sepsis are vague ...

  3. Can Resistin be a New Indicator of Neonatal Sepsis?

    Directory of Open Access Journals (Sweden)

    Didem Aliefendioglu

    2014-02-01

    Conclusion: Resistin levels were higher in premature newborns with sepsis and correlated with IL-6 levels, which is an indicator of neonatal sepsis. This suggests that resistin may also be used in the diagnosis of neonatal sepsis. However, it has limited value when compared with the other inflammatory markers including C-reactive protein, procalcitonin, and IL-6.

  4. Recommendations for sepsis management in resource-limited settings

    NARCIS (Netherlands)

    Dünser, Martin W.; Festic, Emir; Dondorp, Arjen; Kissoon, Niranjan; Ganbat, Tsenddorj; Kwizera, Arthur; Haniffa, Rashan; Baker, Tim; Schultz, Marcus J.

    2012-01-01

    To provide clinicians practicing in resource-limited settings with a framework to improve the diagnosis and treatment of pediatric and adult patients with sepsis. The medical literature on sepsis management was reviewed. Specific attention was paid to identify clinical evidence on sepsis management

  5. The spectrum and outcome of surgical sepsis in Pietermaritzburg ...

    African Journals Online (AJOL)

    sepsis or septic shock from January 2012 to January 2015 were identified. The following criteria (two or more had to be present) were used to identify patients with sepsis: fever (temperature >38.3°C). This open-access article is distributed under. Creative Commons licence CC-BY-NC 4.0. Background. Sepsis is a leading ...

  6. Serum procalcitonin as an early marker of neonatal sepsis

    African Journals Online (AJOL)

    (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. This study was to evaluate the role ... Neonatal sepsis presents a diagnostic problem, as the signs are nonspecific and there is no single reliable .... diagnosis, prognosis and response to treatment of patients with neonatal sepsis.'·' PCT may be a more ...

  7. [Rhodotorula glutinis sepsis. A case report].

    Science.gov (United States)

    Pulvirenti, Fabrizio; Pasqua, Paolo; Falzone, Elio; Maffeo, Federico; Gugliara, Carmelo; Guarneri, Luigi

    2010-06-01

    Fungal sepsis is an important cause of fever resistant to antibiotic therapy that is very often taken into marginal account. It should instead be particularly considered in patients with a long history of immune depression such as diabetes or chronic and debilitating diseases. Blood cultures are essential for diagnostic purposes, preferably performed in antibiotic wash-out, since they may allow identification of pathogenic (or opportunistic) fungi responsible for episodes of fungal sepsis. The case described illustrates an episode of systemic infection by Rhodotorula glutinis correlated with the presence of CVC.

  8. Assessment of Clinical Criteria for Sepsis

    Science.gov (United States)

    Seymour, Christopher W.; Liu, Vincent X.; Iwashyna, Theodore J.; Brunkhorst, Frank M.; Rea, Thomas D.; Scherag, André; Rubenfeld, Gordon; Kahn, Jeremy M.; Shankar-Hari, Manu; Singer, Mervyn; Deutschman, Clifford S.; Escobar, Gabriel J.; Angus, Derek C.

    2016-01-01

    IMPORTANCE The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0–3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected

  9. Kluyvera cryocrescens sepsis in a preterm infant.

    Science.gov (United States)

    Altun Koroglu, Ozge; Yalaz, Mehmet; Ozalkaya, Elif; Polat, Doga Ceren; Akisu, Mete; Kultursay, Nilgun

    2010-05-01

    Kluyvera cryocrescens, formerly accepted as a benign saprophytic microorganism, is an opportunistic pathogen and its infection is very rare in humans. This report describes a preterm infant born at 30 weeks of gestational age and successfully treated for K. cryocrescens sepsis in the 3rd week of life. To our knowledge, this is the first case of K. cryocrescens sepsis in a newborn. The potential of K. cryocrescens as a serious pathogen should be recognized especially in patients such as preterm infants in whom the prognosis may be compromised without appropriate treatment.

  10. Management of Sepsis-Induced Immunosuppression.

    Science.gov (United States)

    Venet, Fabienne; Rimmelé, Thomas; Monneret, Guillaume

    2018-01-01

    It is now well established that profound immunosuppression develops within a few days after sepsis onset in patients. This should be considered additional organ failure because it is associated with increased rate of nosocomial infections, mortality, and long-term complications, thus constituting the rationale for immunomodulation in patients. Nevertheless, the demonstration of the efficacy of such therapeutic strategy in improving deleterious outcomes in sepsis remains to be made. Results from clinical trials based on interleukin 7 and granulocyte macrophage colony-stimulating factor immunoadjuvant therapies in septic shock patients are expected for 2018. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats.

    Science.gov (United States)

    Giustina, Amanda Della; Bonfante, Sandra; Zarbato, Graciela Freitas; Danielski, Lucinéia Gainski; Mathias, Khiany; de Oliveira, Aloir Neri; Garbossa, Leandro; Cardoso, Taise; Fileti, Maria Eduarda; De Carli, Raquel Jaconi; Goldim, Mariana Pereira; Barichello, Tatiana; Petronilho, Fabricia

    2018-02-01

    Sepsis is defined as life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Evidences suggest that oxidative stress is intrinsically related to sepsis progression. Dimethyl fumarate (DMF) is a novel oral therapeutic agent with anti-oxidant properties which exerts protective effects through activation of nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2). Thus, the aim of this study is to evaluate the effect of DMF in different organs of rats submitted to an animal model of sepsis. Adult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) procedure and sham-operated rats was considered control group. The experimental groups were divided into sham + vehicle, sham + DMF, sham + NAC, CLP + vehicle, CLP + DMF, and CLP + NAC. Rats were treated by oral gavage with DMF immediately after and 12 h after surgery, or NAC (s.c.) at 3, 6, and 12 h after surgery. Twenty-four hours after sepsis induction, neutrophil infiltration, nitrite/nitrate concentrations, oxidative damage to lipids and proteins, superoxide dismutase (SOD), and catalase (CAT) activities were evaluated in the heart, liver, lung, and kidney. Septic animals presented increased neutrophil infiltration, NO metabolism, oxidative damage to lipids and proteins, and decreases of SOD and CAT activities, mainly in the heart, liver, and lung, while DMF-treated animals showed significant reduction in neutrophil infiltration, NO metabolism, and oxidative damage followed by increased SOD and CAT activities. DMF is effective in preventing oxidative stress and inflammation in rats 24 h after sepsis induction.

  12. Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults

    Science.gov (United States)

    2014-01-01

    Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better

  13. CAFFEINE IMPROVES HEART RATE WITHOUT IMPROVING SEPSIS SURVIVAL

    Science.gov (United States)

    Bauzá, Gustavo; Remick, Daniel

    2015-01-01

    Introduction Caffeine is consumed on a daily basis for its nervous system stimulant properties and is a global adenosine receptor antagonist. Since adenosine receptors have been found to play a major role in regulating the immune response to a septic insult, we investigated if caffeine consumption prior to a septic insult would alter immunological and physiological responses, as well as survival. Methods Two separate experimental designs were employed, both using outbred female ICR mice. In the first experiment mice were administered 20mg/kg of caffeine (equal to 2–3 cups of coffee for a human) or normal saline intraperitoneally at the time of cecal ligation and puncture (CLP). Immunological parameters including cytokines and local cell recruitment measured. In the second experiment caffeine (10mg/kg/hr) was delivered continuously for 24 hours via a subcutaneous infusion pump placed the day prior to CLP and hemodynamic parameters were examined. In both experiments survival was followed for five days. Results A single dose of caffeine at the initiation of sepsis did not alter survival. This single dose of caffeine did significantly increase in plasma levels of the chemokine KC six hours after the onset of sepsis compared to septic mice given normal saline. There were no changes in IL-6 or IL-10 levels in the caffeine groups. Peritoneal lavages performed 24 hours post-CLP showed no difference in the levels of IL-6, TNF, KC, MIP-1, IL-10 or the IL-1 receptor antagonist between caffeine and normal saline treated mice. Additionally, the lavages yielded similar numbers of cells (4.1×106 vehicle vs. 6.9×106 caffeine) and bacterial colony forming units (CFU, 4.1 million CFU vehicle vs. 2.8 million CFU caffeine). In the infusion group, caffeine also did not alter survival. However, caffeine infusion did increase heart rate prior to CLP, and prevented the decline in heart rate after CLP. Conclusion Caffeine increased heart rate in mice but does not impact cytokine

  14. Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

    Science.gov (United States)

    Thomas, Benjamin S; Jafarzadeh, S Reza; Warren, David K; McCormick, Sandra; Fraser, Victoria J; Marschall, Jonas

    2015-11-24

    Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop

  15. Perioperative treatment of patients with sepsis

    DEFF Research Database (Denmark)

    Ibsen, Michael; Perner, Anders

    2013-01-01

    Key elements in the initial resuscitation and stabilization of the patient with sepsis are fluid therapy, vasopressor or inotropic support, administration of adequate antibiotics and source control. This review will primarily discuss fluid, vasopressor and antibiotic therapy because these have been...

  16. Recurrent Sepsis Caused by Streptococcus pyogenes▿

    OpenAIRE

    Rasmussen, Magnus

    2011-01-01

    I report that a 75-year-old man with severe atherosclerosis experienced two episodes of bacteremia with Streptococcus pyogenes of type emm87. Recurrent sepsis with S. pyogenes is extremely rare, and a foot ulcer was the suspected point of entry. The patient did not develop opsonizing antibodies to the isolate.

  17. Ralstonia picketti neonatal sepsis: a case report.

    Science.gov (United States)

    Sharma, Deepak; Sharma, Pradeep; Soni, Priyanka; Gupta, Basudev

    2017-01-07

    Ralstonia genus are gram negative bacillus and includes four bacteria namely Ralstonia picketti, Ralstonia Solanacearum, Ralstonia insidiosa and Ralstonia mannitolilytica. These are opportunistic pathogens and cause infections in immunocompromised host. The sources of infection are usually contaminated solutions and water. The majority of the reported cases are caused by R. picketti. It is very rare cause of neonatal sepsis with less than twenty cases reported in literature till date. A late preterm male infant, Indian race was admitted to the neonatal intensive care unit for respiratory distress developing soon after birth. The infant was managed with respiratory support and gradually infant improved and diagnosis of transient tachypnea of newborn was made. At age of 84 h of postnatal life, the infant developed features of neonatal sepsis and investigations were suggestive of sepsis. The infant was started on intravenous antibiotic, multiple vasopressors and steroids. The blood culture showed growth of multi-drug resistant R. picketti. The antibiotics were changed as per sensitivity pattern and infant was discharged in good condition and was accepting breast feeding at the time of discharge. There was also no other case of R. picketti in the nursery during the same time period. Ralstonia picketti is an uncommon cause of neonatal sepsis and usually source of infection are contaminated solutions and medical products. The management involves early detection, treatment with appropriate antibiotics and doing surveillance culture to identify the possible source of infection.

  18. Severe sepsis secondary to emphysematous cystitis

    African Journals Online (AJOL)

    M.M. Gargouri

    tures to septic shock. Herein, we present a new case of EC in a patient who presented with severe sepsis in the absence of known risk factors. The patient was also found to have two vesical calculi and a horseshoe kidney. E-mail address: gargourimourad@yahoo.fr (M.M. Gargouri). Peer review under responsibility of Pan ...

  19. Role of critical care in urological sepsis

    Directory of Open Access Journals (Sweden)

    Nagamani Sen

    2006-01-01

    Full Text Available Infections arising from the urinary tract may either elicit a Systemic Inflammatory Response Syndrome or result in Sepsis. This may progress to severe sepsis with associated multi-organ dysfunction and perfusion abnormalities, including hypotension. The mortality associated with sepsis is high, reaching up to 46% in patients with septic shock. Infections arising from the urinary tract may arise either following a primary pathology in the urinary tract or may be acquired as a nosocomial infection. Most of these infections are caused by gram negative organisms, though occasionally gram positive organisms and fungi can infect the urinary tract under certain circumstances. Evaluation of a patient with sepsis should include establishing the diagnosis based on standard criteria, a search for the source and appropriate microbial cultures. Management of these patients requires aggressive fluid resuscitation to achieve well defined goals. This may need to be accompanied by the use of vasopressors and mechanical ventilation. Antimicrobial therapy based on the likely causative organism should be initiated, pending the culture results. Appropriate source control measures should also be taken. Prompt recognition, aggressive resuscitation and appropriate source control measures along with appropriate antimicrobial therapy will help to reduce the mortality in patients with urosepsis.

  20. Diagnostic value of procalcitonin in neonatal sepsis

    African Journals Online (AJOL)

    neonatal sepsis. Accepted: 27th April 2015. Arowosegbe AO. Ojo DA, Shittu OB. Department of Microbiology,. Federal University of Agriculture,. Alabata ..... 0.031. Refusal to Feed. Present. Absent. 23. 62. 06 (26.1%). 24 (38.7%). 17 (73.9%). 38 (61.3%). 0.279. *Outcome of. Management. Discharge. Death. 48. 27. 26 (54.2 ...

  1. Sepsis in Solid-Organ Transplant Patients.

    Science.gov (United States)

    Bafi, Antônio Tonete; Tomotani, Daniere Yurie Vieira; de Freitas, Flávio Geraldo Rezende

    2017-01-01

    The growing population of solid organ transplant (SOT) recipients is at a significantly increased risk for developing infections. In some patients, the infection can lead to a dysregulated systemic inflammatory response with acute organ dysfunction. SOT recipients with sepsis tend to have less fever and leukocytosis instances. Moreover, they have diminished symptoms and attenuated clinical and radiologic findings. The current management of sepsis is similar to general patients. It relies mainly on early recognition and treatment, including appropriate administration of antibiotics and resuscitation with intravenous fluids and vasoactive drugs when needed. The infusion of fluids should be closely monitored because elevated central venous pressure levels and fluid overload can be particularly harmful. There is no consensus on how to manage immunosuppressive therapies during sepsis, although dose reduction or withdrawal is suggested to improve the host immunological response. There is compelling evidence suggesting that infections are associated with reduced allograft and patient survival. However, the traditional belief that SOT patients who develop sepsis have worse outcomes than non-transplanted patients has been challenged.

  2. Pemberian Antitrombin III pada Sepsis Neonatal

    Directory of Open Access Journals (Sweden)

    Nathanne Septhiandi

    2016-11-01

    Kesimpulan. Secara statistik penggunaan AT III apabila dibandingkan dengan plasebo pada keadaan sepsis neonatal tidak memperbaiki prognosis dalam hal menurunkan tingkat mortalitas selama 28-30 hari. Walaupun demikian, tingkat mortalitas kelompok AT III lebih rendah dibandingkan dengan placebo.

  3. Inhibition of indoleamine 2,3-dioxygenase 1/2 prevented cognitive impairment and energetic metabolism changes in the hippocampus of adult rats subjected to polymicrobial sepsis.

    Science.gov (United States)

    Comim, Clarissa M; Freiberger, Viviane; Ventura, Letícia; Mina, Francielle; Ferreira, Gabriela K; Michels, Monique; Generoso, Jaqueline S; Streck, Emílio L; Quevedo, João; Barichello, Tatiana; Dal-Pizzol, Felipe

    2017-04-15

    Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that may affect the brain. We investigated the role of indoleamine 2,3-dioxygenase (IDO-1/2) inhibition on long-term memory and energetic metabolism after experimental sepsis by caecal ligation and perforation (CLP). Experimental sepsis increased the activity of complexes I, II-III and IV at 24h after CLP, and IDO-1/2 inhibition normalized the activity of these complexes in the hippocampus. Wistar rats presented impairment of habituation and aversive memories 10days after CLP. Adjuvant treatment with the IDO inhibitor prevented long-term cognitive impairment triggered by sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

    Science.gov (United States)

    Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

    2017-09-01

    Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

  5. Translational research and biomarkers in neonatal sepsis.

    Science.gov (United States)

    Delanghe, Joris R; Speeckaert, Marijn M

    2015-12-07

    As neonatal sepsis is a severe condition, there is a call for reliable biomarkers to differentiate between infected and noninfected newborns. Although blood culture has been considered as the gold standard, this analysis is still too slow and limited by false negative results. Use of CRP is hampered by a physiological 3-day increase, resulting in a low sensitivity to detect sepsis at an early stage. A moderate diagnostic accuracy of other acute phase proteins has been demonstrated (serum amyloid A, procalcitonin, lipopolysaccharide binding protein, mannose binding lectin and hepcidin). In neonatal sepsis, changed chemokine/cytokine levels are observed before those of acute phase reactants. High IL-6, IL-8, IL-10 and TNF-α concentrations are detected in infected infants. Soluble interleukin-2 receptor has been used to identify bacteremia, whereas low plasma RANTES concentrations are characteristic for septicemia. Several cell adhesion molecules contribute to the pathogenesis of sepsis. As an upregulated CD64 expression on granulocytes is found within 1-6h after bacterial invasion, serial CD64 measurements could guide antibiotic therapy. An increased CD11b/CD18 density can improve the diagnosis, and a positive correlation between CD11b and the severity of systemic inflammation has been reported. An early increase in sCD14-ST presepsin is also observed during sepsis, whereas high sTREM-1 values in early-onset neonatal sepsis (EOS) have been associated with mortality. Biomarkers resulting from proteomics are also promising. A 4-biomarker 'mass restricted' score has been validated as diagnostic for intra-amniotic infection and/or inflammation. S100A8 in amniotic fluid is a strong predictor of an increased incidence of EOS. Proteomic analysis of cord blood has revealed altered protein expression patterns. The ApoSAA score is useful for identifying sepsis and could guide prescription of antibiotics. (1)H-NMR and GC-MS metabolomics allow to diagnose septic shock, which is

  6. Identifying Patients With Sepsis on the Hospital Wards.

    Science.gov (United States)

    Bhattacharjee, Poushali; Edelson, Dana P; Churpek, Matthew M

    2017-04-01

    Sepsis contributes to up to half of all deaths in hospitalized patients, and early interventions, such as appropriate antibiotics, have been shown to improve outcomes. Most research has focused on early identification and treatment of patients with sepsis in the ED and the ICU; however, many patients acquire sepsis on the general wards. The goal of this review is to discuss recent advances in the detection of sepsis in patients on the hospital wards. We discuss data highlighting the benefits and limitations of the systemic inflammatory response syndrome (SIRS) criteria for screening patients with sepsis, such as its low specificity, as well as newly described scoring systems, including the proposed role of the quick sepsis-related organ failure assessment (qSOFA) score. Challenges specific to detecting sepsis on the wards are discussed, and future directions that use big data approaches and automated alert systems are highlighted. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  7. Redox therapy in neonatal sepsis: reasons, targets, strategy, and agents.

    Science.gov (United States)

    Bajčetić, Milica; Spasić, Snežana; Spasojević, Ivan

    2014-09-01

    Neonatal sepsis is one of the most fulminating conditions in neonatal intensive care units. Antipathogen and supportive care are administered routinely, but do not deliver satisfactory results. In addition, the efforts to treat neonatal sepsis with anti-inflammatory agents have generally shown to be futile. The accumulating data imply that intracellular redox changes intertwined into neonatal sepsis redox cycle represent the main cause of dysfunction of mitochondria and cells in neonatal sepsis. Our aim here is to support the new philosophy in neonatal sepsis treatment, which involves the integration of mechanisms that are responsible for cellular dysfunction and organ failure, the recognition of the most important targets, and the selection of safe agents that can stop the neonatal sepsis redox cycle by hitting the hot spots. Redox-active agents that could be beneficial for neonatal sepsis treatment according to these criteria include lactoferrin, interleukin 10, zinc and selenium supplements, ibuprofen, edaravone, and pentoxifylline.

  8. Clinical analysis of cases of neonatal Streptococcus agalactiae sepsis.

    Science.gov (United States)

    Zeng, S J; Tang, X S; Zhao, W L; Qiu, H X; Wang, H; Feng, Z C

    2016-06-17

    With the advent of antibiotic resistance, pathogenic bacteria have become a major threat in cases of neonatal sepsis; however, guidelines for treatment have not yet been standardized. In this study, 15 cases of neonatal Streptococcus agalactiae sepsis from our hospital were retrospectively analyzed. Of these, nine cases showed early-onset and six cases showed late-onset sepsis. Pathogens were characterized by genotyping and antibiotic sensitivity tests on blood cultures. Results demonstrated that in cases with early-onset sepsis, clinical manifestations affected mainly the respiratory tract, while late-onset sepsis was accompanied by intracranial infection. Therefore, we suggest including a cerebrospinal fluid examination when diagnosing neonatal sepsis. Bacterial genotyping indicated the bacteria were mainly type Ib, Ia, and III S. agalactiae. We recommend treatment with penicillin or ampicillin, since bacteria were resistant to clindamycin and tetracycline. In conclusion, our results provide valuable information for the clinical treatment of S. agalactiae sepsis in neonatal infants.

  9. Neonatal sepsis: an old problem with new insights.

    Science.gov (United States)

    Shah, Birju A; Padbury, James F

    2014-01-01

    Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBWneonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter α inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount.

  10. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    Science.gov (United States)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

  11. [New Sepsis-3 definition : Do we have to treat sepsis before we can diagnose it from now on?

    Science.gov (United States)

    Schmoch, T; Bernhard, M; Uhle, F; Gründling, M; Brenner, T; Weigand, M A

    2017-05-11

    The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) have been available since the beginning of 2016. SEPSIS-3 completely replaces the old SIRS criteria in the definition of sepsis and defines sepsis from now on as "life-threatening organ dysfunction caused by a dysregulated host response to infection". However, it seems questionable whether in clinical practice the new definition is really superior to the old one. The most important question is the following: Is it helpful to have a definition that first recognizes a patient once organ dysfunction has occurred and the patient already needs intensive care?

  12. A computational approach to early sepsis detection.

    Science.gov (United States)

    Calvert, Jacob S; Price, Daniel A; Chettipally, Uli K; Barton, Christopher W; Feldman, Mitchell D; Hoffman, Jana L; Jay, Melissa; Das, Ritankar

    2016-07-01

    To develop high-performance early sepsis prediction technology for the general patient population. Retrospective analysis of adult patients admitted to the intensive care unit (from the MIMIC II dataset) who were not septic at the time of admission. A sepsis early warning algorithm, InSight, was developed and applied to the prediction of sepsis up to three hours prior to a patient's first five hour Systemic Inflammatory Response Syndrome (SIRS) episode. When applied to a never-before-seen set of test patients, InSight predictions demonstrated a sensitivity of 0.90 (95% CI: 0.89-0.91) and a specificity of 0.81 (95% CI: 0.80-0.82), exceeding or rivaling that of existing biomarker detection methods. Across predictive times up to three hours before a sustained SIRS event, InSight maintained an average area under the ROC curve of 0.83 (95% CI: 0.80-0.86). Analysis of patient sepsis risk showed that contributions from the coevolution of multiple risk factors were more important than the contributions from isolated individual risk factors when making predictions further in advance. Sepsis can be predicted at least three hours in advance of onset of the first five hour SIRS episode, using only nine commonly available vital signs, with better performance than methods in standard practice today. High-order correlations of vital sign measurements are key to this prediction, which improves the likelihood of early identification of at-risk patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Autophagy and skeletal muscles in sepsis.

    Directory of Open Access Journals (Sweden)

    Mahroo Mofarrahi

    Full Text Available Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, or inefficient cellular components. No information is available regarding the degree of sepsis-induced mitochondrial injury and autophagy in the ventilatory and locomotor muscles. This study tests the hypotheses that the locomotor muscles are more prone to sepsis-induced mitochondrial injury, depressed biogenesis and autophagy induction compared with the ventilatory muscles.Adult male C57/Bl6 mice were injected with i.p. phosphate buffered saline (PBS or E. coli lipopolysaccharide (LPS, 20 mg/kg and sacrificed 24 h later. The tibialis anterior (TA, soleus (SOLD and diaphragm (DIA muscles were quickly excised and examined for mitochondrial morphological injury, Ca(++ retention capacity and biogenesis. Autophagy was detected with electron microscopy, lipidation of Lc3b proteins and by measuring gene expression of several autophagy-related genes. Electron microscopy revealed ultrastructural injuries in the mitochondria of each muscle, however, injuries were more severe in the TA and SOL muscles than they were in the DIA. Gene expressions of nuclear and mitochondrial DNA transcription factors and co-activators (indicators of biogenesis were significantly depressed in all treated muscles, although to a greater extent in the TA and SOL muscles. Significant autophagosome formation, Lc3b protein lipidation and upregulation of autophagy-related proteins were detected to a greater extent in the TA and SOL muscles and less so in the DIA. Lipidation of Lc3b and the degree of induction of autophagy-related proteins were significantly blunted in mice expressing a muscle-specific IκBα superrepresor.We conclude that locomotor muscles are more prone to sepsis-induced mitochondrial injury, decreased biogenesis and increased autophagy compared with the

  14. Severe Puerperal Sepsis-A Simmering Menace.

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    Marwah, Sheeba; Topden, Sonam R; Sharma, Manjula; Mohindra, Ritin; Mittal, Pratima

    2017-05-01

    Even decades after the development of effective low-cost antibiotics, sepsis persists as the foremost cause of preventable maternal death worldwide. In developing countries like India, where the paramount impediment to intervention is poverty, maternal mortality due to sepsis is a continuing representation of maternal health inequality. To determine the incidence, risk factors and mortality in women presenting with puerperal sepsis in a tertiary care health facility in India. This retrospective study was carried out in VMMC and Safdarjung Hospital, New Delhi, India, from January 2016 to June 2016 in Department of Obstetrics and Gynaecology. Case records of all eligible patients of puerperal sepsis were reviewed and data were extracted regarding demographic profile, clinical profile on admission, course in hospital, management, complications and cause of mortality (in case of death). Inclusion criteria were any patient presenting either immediately after delivery or miscarriage or within 42 days of these events with fever and any of the following: pain abdomen, malodorous lochia, abdominal distention, uterine tenderness, pelvic abscess, peritonitis, mechanical or foreign body injury, any system/organ failure or shock. Exclusion criteria consisted of patients presenting with fever during pregnancy or more than 42 days after delivery or miscarriage, or patients presenting with fever due to medical conditions, wound infection, mastitis, UTI or thrombophlebitis. Data were entered in predesigned proformas and analysed. A p-value of less than 0.05 was considered significant. During the study period, a total of 33 cases met the inclusion criteria. Of these, 90% were referred cases. Anaemia, prolonged labour, delivery by an untrained person and unsafe abortion were the main identifiable risk factors. Surgical management was required in 75% cases, while 70% women succumbed to their illness, mostly due to multiorgan failure. Maternal mortality due to maternal sepsis is very

  15. Sepsis-related mortality in 497 cases with blood culture-positive sepsis in an emergency department.

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    Rannikko, Juha; Syrjänen, Jaana; Seiskari, Tapio; Aittoniemi, Janne; Huttunen, Reetta

    2017-05-01

    Few studies have sought to establish how often death after sepsis is related to the sepsis and how often underlying diseases have a major role in case fatality. In this retrospective cohort study, data were collected on 497 cases with blood culture-positive sepsis in an emergency department (ED). Sepsis was categorized as severe in 31% of cases; 7% had septic shock. The quick Sepsis-related Organ Failure Assessment score was positive in 136 out of 473 cases (29%). Ninety-eight patients died by day 90; in 16 of these cases (16%) the death was sepsis-related in a patient without a rapidly fatal underlying disease, in 45 cases (46%) the death was sepsis-related in a patient with a rapidly fatal underlying disease, and in 37 cases (38%) the death was unrelated to sepsis. Sepsis-related death occurred in 58 out of 61 cases (95%) by day 28. Underlying diseases were found to have a considerable role in the death of patients suffering from blood culture-positive sepsis in an ED of a developed country, as only 16% of the deaths by day 90 occurred where death was sepsis-related and the patient had a life-expectancy of more than 6 months. Improving the outcome of sepsis with new treatments is thus challenging. It is possible that day 7+day 28 mortality is a more appropriate endpoint than day 90 mortality when studying the outcome of sepsis, as this time-span includes most of the patients whose death was related to sepsis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

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    Alexander D Malkin

    2015-10-01

    Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

  17. CE: Managing Sepsis and Septic Shock: Current Guidelines and Definitions.

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    Makic, Mary Beth Flynn; Bridges, Elizabeth

    2018-02-01

    : Sepsis is a leading cause of critical illness and hospital mortality. Early recognition and intervention are essential for the survival of patients with this syndrome. In 2002, the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) launched the Surviving Sepsis Campaign (SSC) to reduce overall patient morbidity and mortality from sepsis and septic shock by driving practice initiatives based on current best evidence. The SSC guidelines have been updated every four years, with the most recent update completed in 2016. The new guidelines have increased the focus on early identification of infection, risks for sepsis and septic shock, rapid antibiotic administration, and aggressive fluid resuscitation to restore tissue perfusion.In 2014, the SCCM and the ESICM convened a task force of specialists to reexamine the definitions of terms used to identify patients along the sepsis continuum. In 2016, this task force published the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The new definitions and recommendations included tools, based on an updated understanding of the pathobiology of sepsis, that can be used to predict adverse outcomes in patients with infection.This article discusses the new SSC treatment guidelines, changes in the sepsis bundle interventions, and the Sepsis-3 definitions and tools, all of which enable nurses to improve patient outcomes through timely collaborative action.

  18. Can melatonin be used as a marker for neonatal sepsis?

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    El-Mashad, Abdel-Rahman; Elmahdy, Heba; El-Dib, Mohamed; Elbatch, Manal; Aly, Hany

    2016-09-01

    Melatonin, an indolamine endogenously produced by pineal body, has important role as an anti-oxidant, anti-inflammatory and anti-apoptotic. Whether melatonin concentration changes in neonatal sepsis and whether it can be used as a marker of sepsis is unknown. The objective of this study is to evaluate melatonin concentration in the serum as a marker for neonatal sepsis and compare it to standard markers. We prospectively studied 40 neonates: 20 diagnosed with late neonatal sepsis and 20 healthy neonates as a control group. Markers of sepsis and melatonin concentration were compared between both groups. The sepsis groups had significantly increased immature to total neutrophils ratio (I/T ratio), and high sensitivity C-reactive protein (HsCRP), and decreased platelet count. Melatonin concentration was increased in sepsis group when compared to control group (27.2 ± 3.3 versus 11.4 ± 3.2 pg/ml, p = 0.001), and positively correlated with HsCRP (r = 0.952, p = 0.001) and I/T ratio (r = 0.326, p = 0.015). Combining melatonin to HsCRP increased sensitivity and specificity to detect neonatal sepsis to 97.3 and 93.3%, respectively. Endogenous melatonin concentration is increased in late neonatal sepsis and can potentially be used as a marker for sepsis especially when combined with CRP.

  19. [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.

  20. Sepsis and multiorgan failure following TVT procedure.

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    Stec, Piotr; Connell, Rowan

    2014-04-01

    Tension-free vaginal tape (TVT), is a commonly performed, low risk procedure for treatment of stress urinary incontinence (SUI). Severe complications are rare, but can be potentially life threatening. We present a case of 66 year old patient who sustained bladder perforation at the time of TVT procedure and subsequently developed sepsis rapidly leading to multi-organ failure and triggering sequence of serious complications. During her inpatient stay she required ITU admission, emergency laparotomy, TVT mesh removal, bowel resection due to ischemic colitis and anticoagulation for pulmonary embolism. Despite of clinical picture of sepsis her microbiology tests were almost consistently negative. This case emphasise importance of awareness and quick recognition of TVT related complications. Patient ultimately survived and recovered thanks to timely and coordinated management by the multidisciplinary team of doctors.

  1. Risk assessment in neonatal early onset sepsis.

    Science.gov (United States)

    Mukhopadhyay, Sagori; Puopolo, Karen M

    2012-12-01

    The incidence of neonatal early onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early onset sepsis remains a potentially fatal condition, particularly among very low birth-weight infants. Clinical signs of neonatal infection are nonspecific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Apoptosis: Therapeutic target in neurodegeneration and sepsis

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    Gonzalo Arboleda

    2005-12-01

    Full Text Available Cellular apoptosis has been considered as themain physiological mechanism underlyingneuronal demise associated to neurodegenerativediseases. Apoptosis has also been described inparenquimal and microvascular endotheliumin the acute phase of sepsis during multi-organicdysfunction. Therefore, strategies aimed toMuerte celular: blanco terapéutico enneurodegeneración y sepsisGonzalo Arboleda*, Luisa M. Matheus†prevent apoptosis (anti-apoptotic represent avaluable tool for prevention and/or retardationof the appearance of clinical symptoms in thesedisorders, which generate a large morbilitymortality,social and economic burden worldwide.The present review is aim to show that antiapoptoticstrategies hold a great therapeuticpotential. In this sense, we will review some ofthese potential therapies such as caspaseinhibitors, activated protein C, Bcl-2 family andthe PI3K/Akt signalling pathway.

  3. Biomarkers for sepsis: past, present and future

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    Giuseppe Chesi

    2016-12-01

    Full Text Available Sepsis is a complication of severe infection associated with high mortality and open diagnostic issues. Treatment strategies are currently limited and essentially based on prompt recognition, aggressive supportive care and early antibiotic treatment. In the last years, extensive antibiotic use has led to selection, propagation and maintenance of drug-resistant microorganisms. In this context, several biomarkers have been proposed for early identification, etiological definition, risk stratification and improving antibiotic stewardship in septic patient care. Among these molecules, only a few have been translated into clinical practice. In this review, we provided an updated overview of established and developing biomarkers for sepsis, focusing our attention on their pathophysiological profile, advantages, limitations, and appropriate evidence-based use in the management of septic patients.

  4. Hemostasis biomarkers and risk of sepsis: the REGARDS cohort.

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    Moore, J X; Zakai, N A; Mahalingam, M; Griffin, R L; Irvin, M R; Safford, M M; Baddley, J W; Wang, H E

    2016-11-01

    Essentials Few studies have investigated the risk of sepsis by baseline hemostasis biomarkers measures. Baseline hemostasis biomarkers and risk of sepsis was examined using case-control study design. Increased fibrinogen, factor IX, and factor XI levels may be associated with risk of sepsis. Hemostasis biomarkers may provide a target for sepsis mitigation or prevention. Background Sepsis is a major public health concern, responsible for more than 750 000 hospitalizations and 200 000 annual deaths in the USA. Few studies have investigated the association between baseline measurements of hemostasis biomarkers and the future risk of sepsis. Objective To determine whether hemostasis biomarkers levels measured at baseline in a cohort of community-dwelling participants are associated with the risk of future sepsis events. Methods We performed a nested case-control study within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We identified sepsis hospitalizations occurring over a 10-year period. There were 50 incident sepsis cases with baseline measurements of hemostasis (fibrinogen, factor VIII, FIX, FXI, protein C, and D-dimer). Using incidence density sampling, we matched the 50 sepsis cases with 200 controls by age, sex, and race. We used conditional logistic regression to evaluate the association between baseline hemostasis biomarkers and future sepsis events. Results Comparison of 50 sepsis cases with 200 non-sepsis controls showed that sepsis cases had lower education and income, were more likely to live in the stroke belt, had chronic lung disease, and had higher albumin level/creatinine level ratios (ACRs). Individuals with higher baseline fibrinogen levels (adjusted odds ratio [OR] per standard deviation: 1.40, 95% confidence interval [CI] 1.01-1.94), FIX levels ([OR] 1.46, 95% [CI] 1.03-2.07) and FXI levels ([OR]1.52, 95% [CI] 1.04-2.23) were more likely to experience a sepsis event. Conclusion Baseline fibrinogen, FIX and FXI

  5. Metabolic changes in cardiomyocytes during sepsis

    OpenAIRE

    Douglas, James J.; Walley, Keith R.

    2013-01-01

    Different types of shock induce distinct metabolic changes. The myocardium at rest utilizes free fatty acids as its primary energy source, a mechanism that changes to aerobic glycolysis during sepsis and is in contrast to hemorrhagic shock. The immune system also uses this mechanism, changing its substrate utilization to activate innate and adaptive cells. Cardiomyocytes share a number of features similar to antigen-presenting cells and may use this mechanism to augment the immune response at...

  6. Metabolic changes in cardiomyocytes during sepsis.

    Science.gov (United States)

    Douglas, James J; Walley, Keith R

    2013-09-20

    Different types of shock induce distinct metabolic changes. The myocardium at rest utilizes free fatty acids as its primary energy source, a mechanism that changes to aerobic glycolysis during sepsis and is in contrast to hemorrhagic shock. The immune system also uses this mechanism, changing its substrate utilization to activate innate and adaptive cells. Cardiomyocytes share a number of features similar to antigen-presenting cells and may use this mechanism to augment the immune response at the reversible expense of cardiac function.

  7. Neonatal sepsis: progress towards improved outcomes.

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    Shane, Andi L; Stoll, Barbara J

    2014-01-01

    Neonates are predisposed to infections during the perinatal period due to multiple exposures and a relatively compromised immune system. The burden of disease attributed to neonatal infections varies by geographic region and maternal and neonatal risk factors. Worldwide, it is estimated that more than 1.4 million neonatal deaths annually are the consequence of invasive infections. Risk factors for early-onset neonatal sepsis (EOS) include prematurity, immunologic immaturity, maternal Group B streptococcal colonization, prolonged rupture of membranes, and maternal intra-amniotic infection. Intrapartum antimicrobial prophylaxis administered to GBS-colonized women has reduced the burden of disease associated with early onset GBS invasive infections. Active surveillance has identified Gram-negative pathogens as an emerging etiology of early-onset invasive infections. Late-onset neonatal sepsis (LOS) attributable to Gram-positive organisms, including coagulase negative Staphylococci and Staphylococcus aureus, is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of late-onset sepsis, especially among infants who receive broad spectrum antimicrobial agents. Prophylactic fluconazole administration to very low birthweight (VLBW) neonates during the first 6 weeks of life reduces invasive candidiasis in neonatal intensive care units with high rates of fungal infection. Prevention of healthcare associated infections through antimicrobial stewardship, limited steroid use, early enteral feeding, limited use of invasive devices and standardization of catheter care practices, and meticulous hand hygiene are important and cost-effective strategies for reducing the burden of late-onset neonatal sepsis. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  8. In vitro diagnosis of sepsis: a review

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    Guido M

    2016-03-01

    Full Text Available Marcello Guido,1 Maria Rosaria Tumolo,2 Antonella De Donno,1 Tiziano Verri,3 Francesca Serio,1 Francesco Bagordo,1 Antonella Zizza2 1Laboratory of Hygiene, Department of Biological and Environmental Sciences and Technologies, Faculty of Sciences, University of Salento, Lecce, Italy; 2National Research Council, Institute of Clinical Physiology, 3Laboratory of Physiology, Department of Biological and Environmental Sciences and Technologies, Faculty of Sciences, University of Salento, Lecce, ItalyAbstract: Sepsis, severe sepsis and septic shock, systemic inflammatory response, and other related manifestations represent a relevant medical problem with high morbidity and mortality, despite the improvements in diagnosis, treatment, and preventive measures over the last few decades. The limited knowledge of the pathophysiology in association with the lack of in vitro diagnostic methods for the certain and quick determination of the causative microbiological agents and their antibiotic resistance means the condition is still critical and of high impact in health care. The current gold standard method to detect the sepsis-causing pathogens, which is based on blood culture, is still insufficiently sensitive and slow. The new culture-independent molecular biology-based techniques can lead to the identification of a broad range of microorganisms and resistance markers within a few hours and with high sensitivity and specificity; nevertheless, limitations of, for example, the polymerase chain reaction-based methods still hamper their application in the clinical routine. This review summarizes the in vitro diagnostic methods and their approach in the clinical diagnosis of the bloodstream infections, and explores their advantages and disadvantages at the current state of the art. A quick analysis of the future prospective in multiplex technologies for microbiological diagnosis of sepsis is also provided. Keywords: PCR, PCR/ESI-MS, microarray, MALDI-TOF, next

  9. Anticoagulación y sepsis, la oportunidad para un nuevo uso de la heparina?

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    Fabián Jaimes

    2006-03-01

    Full Text Available La sepsis es una causa importante de morbilidad y mortalidad alrededor del mundo, y la magnitud del problema parece mayor en los países en desarrollo. En las últimas dos décadas, el tratamiento estándar sólo ha resultado en una disminución discreta de la mortalidad, y esa disminución ha sido opacada por un incremento de casi 300% en su incidencia. Recientemente se ha documentado la relación estrecha entre la infección, la inflamación y la coagulación en la sepsis; y, aunque la coagulación intravascular diseminada puede ocurrir en sólo 30% a 50% de los pacientes, la activación de la cascada de la coagulación es una respuesta temprana y común ante casi cualquier reto infeccioso. Así mismo, la mayoría de las moléculas involucradas en el estado procoagulante que caracteriza la sepsis son también amplificadores o generadores de la respuesta inflamatoria. Estos hallazgos han impulsado la investigación de productos biológicos con actividad anticoagulante como terapia adicional para pacientes con los estados más graves del síndrome de sepsis. Esta revisión explica los aspectos biológicos y moleculares que soportan el uso potencial de los tratamientos anticoagulantes en sepsis, y analiza la evidencia experimental y de estudios preclínicos que sugiere la utilidad de la heparina como un tratamiento complementario eficaz en todos los estados clínicos de la entidad.

  10. Fatal early-onset neonatal sepsis due to Streptococcus pneumoniae.

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    Nallusamy, R

    1998-12-01

    Two cases of invasive early-onset neonatal pneumococcal sepsis are reported. One neonate was born at term with no risk factors and the other preterm at 35 weeks. Sepsis was not detected at birth for either of these babies and diagnosis was made at the stage of severe sepsis. A fatal outcome resulted despite treatment. Pneumococcal sepsis was confirmed after death in both these cases. Although maternal carriage was not documented in either case, the ages at presentation and progression suggested perinatal acquisition of infection. Early onset neonatal pneumococcal sepsis presents similarly as early onset neonatal Group B streptococcal (GBS) sepsis. Vaginal carriage of pneumococcus is rare but the micro-organism may have a higher invasion to colonisation ratio (attack rate) than GBS. Risk factors for invasive disease are similar to GBS.

  11. Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

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    Delano, Matthew J.; Ward, Peter A.

    2016-01-01

    Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after “recovery” from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical “recovery,” with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved. PMID:26727230

  12. Sepsis as a cause of intrahepatic cholestasis

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    Rudić Jelena

    2009-01-01

    Full Text Available Introduction. The causes of intrahepatic cholestasis include cholestatic viral hepatitis, primary biliary cirrhosis, benign recurrent cholestasis, primary sclerosing cholangitis and sepsis. During sepsis, proinflammatory cytokines and nitric oxide cause cholestasis by impairing hepatocellular and ductal bile formation. Case Outline. We report a 48-year-old woman who was admitted to hospital due to malaise, jaundice, fever and pain in the neck. Physical examination revealed jaundice, tachycardia (pulse rate was 120/min, hypotension 90/60 mm Hg. Laboratory findings showed normocytic normochromic anaemia, inflammatory syndrome and abnormal liver function tests indicating cholestasis and hepatocellular necrosis. Abdominal ultrasonography detected hepatosplenomegaly. Chest computed tomography showed bronchopneumonic infiltrates. Percutaneous liver biopsy was performed using a Menghini needle of 1.4 mm. Pathohystological analysis of the liver tissue confirmed reactive, intrahepatic cholestasis. Blood cultures isolated Staphylococcus aureus. After the diagnosis was established the treatment with broad-spectrum antibiotics was carried out, resulting in the improvement of general condition of the patient, regression of inflammatory syndrome, disappearance of cholestasis and regression of pulmonary infiltrates. Abdominal ultrasonography after antibiotic treatment did not show hepatosplenomegaly. Conclusion. Concerning patients with cholestasis of uncertain origin, we should always think of sepsis as a possible cause in order to start antibiotic treatment in time.

  13. Clinical significance of soluble Fas plasma levels in patients with sepsis

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    Mikić Dragan

    2015-01-01

    Full Text Available Background/Aim. The goal of modern clinical and experimental researches in the field of sepsis is to find one or more sensitive parameters that could predict the severity of sepsis and its outcome. In this study we investigated and compared the relationship of initial soluble Fas (sFas plasma levels as well as Acute Physiology, Age and Chronic Health Evaluation II (APACHE II score in 58 septic patients with severity and outcome of sepsis. Methods. The diagnosis and assessment of disease severity was performed on the same day, based on clinical and laboratory parameters. The blood samples were used for monitoring of laboratory standard parameters necessary for the diagnosis of sepsis, organ dysfunction and assessment of disease severity, as well as for determination of levels of sFas. According to consensus criteria, patients were divided into those with sepsis (n = 16, severe sepsis (n = 30 or septic shock (n = 12, those with (n = 26 and without (n = 32 multiple organ dysfunction syndrome (MODS, and survivors (n = 45 and non-survivors (n = 13. Results. Plasma sFas level (9.7 ± 10.1; 0-44.2 U/mL was elevated in 54.4% of patients. All the patients with septic shock, 76.9% of the patients with MODS and 84.6% patients who died had elevated sFas level. We observed a strong positive correlation between sFas and APACHE II score (p < 0.001. The level of sFas was significantly higher in patients with septic shock compared to normotensive patients (p < 0.001, patients with MODS compared to those without MODS (p < 0.001 and survivors compared to nonsurvivors (p < 0.01. Conclusions. Our results suggest that initial sFas plasma levels in patients with sepsis correlated with the values of APACHE II score and separated very well the patients with septic shock versus the normotensive patients, the patients with and without MODS, and survivors versus non-survivors.

  14. Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors.

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    Ree, Isabelle M C; Fustolo-Gunnink, Suzanne F; Bekker, Vincent; Fijnvandraat, Karin J; Steggerda, Sylke J; Lopriore, Enrico

    2017-01-01

    Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. A cohort study was carried out among all neonates with proven culture positive sepsis that were admitted to a tertiary NICU between 2006 and 2015 (n = 460). The occurrence, severity and duration of thrombocytopenia were recorded, as well as major bleedings and potential risk factors for mortality in neonatal sepsis. Sepsis was diagnosed in 460 of 6551 neonates (7%). Severe thrombocytopenia (platelets ≤50*109/L) occurred in 20% (92/460) of septic neonates. The median time for platelets to rise >100*109 was 6.0 days (interquartile range 4.0-7.0). On multivariate analysis, maternal hypertension, intravascular thrombosis and Gram negative (as opposed to Gram positive) sepsis were independently associated with thrombocytopenia in neonatal sepsis. In severe thrombocytopenia, 10% (9/92) suffered a severe IVH, compared to 5% (20/356) in neonates with platelets >50*109/L (p = 0.125). 10% (9/92) suffered a pulmonary hemorrhage, compared to 2% (9/368) in neonates with platelets >50*109/L (p = 0.001). On multivariate analysis, thrombocytopenia and Gram negative (as opposed to Gram positive) sepsis were independently associated with neonatal mortality. Thrombocytopenia is independently associated with maternal hypertension, intravascular thrombosis and Gram negative sepsis. Thrombocytopenia in neonatal sepsis increases the risk of mortality nearly four-fold, with another six-fold increase in mortality in case of Gram negative sepsis.

  15. THE STUDY OF SERUM PROCALCITONIN LEVEL IN CORRELATION WITH SEPSIS

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    Girish M

    2016-09-01

    Full Text Available BACKGROUND Sepsis refers to the systemic response to serious infection. It can be response to the infection caused by any class of microorganism. The presence of bacteraemia is an indicator of disseminated infection and generally indicates a poorer prognosis when associated with localised disease. This study was undertaken to study the diagnostic and prognostic value of Procalcitonin (PCT in patients with sepsis. AIM To study the diagnostic and prognostic value of Procalcitonin (PCT in patients with sepsis. MATERIALS AND METHODS Fifty patients of age more than 18 years with sepsis admitted in KMC Hospitals, Mangalore, from August 2008 to June 2010 were subjects in the study after due permission from institution and informed consent from the patients. Diagnosis of sepsis was made according to criteria by ACCP/SCCM definition for sepsis. Definitive aetiological diagnosis requires isolation of microorganism from the blood and local site of infection, Gram stain and culture of the material from the primary site of infection for the microbial aetiology was taken. Other appropriate laboratory investigations depending upon requirement were done as mentioned in the investigations. RESULTS Out of total 50 patients, 23 patients were in group of sepsis, 14 were in group of severe sepsis while 13 had septic shock. Maximum number of the study patients were in the age group of 51-60 years. 52% of the study patients were male and 48% were female. Most common symptom in patients with sepsis was fever. Most common sign in the patient with sepsis is tachycardia followed by high temperature and then tachypnoea. Most common source of sepsis was respiratory infection followed by UTI. CONCLUSION Our data suggest the possibility that the addition of Procalcitonin into the standard workup of critically ill patients with suspected sepsis could increase diagnostic certainty and improve patient management.

  16. Characterising Cytokine Gene Expression Signatures in Patients with Severe Sepsis

    OpenAIRE

    Grealy, Robert; White, Mary; Stordeur, Patrick; Kelleher, Dermot; Doherty, Derek G.; McManus, Ross; Ryan, Thomas

    2013-01-01

    PUBLISHED Introduction. Severe sepsis in humans may be related to an underlying profound immune suppressive state. We investigated the link between gene expression of immune regulatory cytokines and the range of illness severity in patients with infection and severe sepsis. Methods. A prospective observational study included 54 ICU patients with severe sepsis, 53 patients with infection without organ failure, and 20 healthy controls. Gene expression in peripheral blood mononuclear cells (P...

  17. Mass spectrometry for the discovery of biomarkers of sepsis.

    Science.gov (United States)

    Ludwig, Katelyn R; Hummon, Amanda B

    2017-03-28

    Sepsis is a serious medical condition that occurs in 30% of patients in intensive care units (ICUs). Early detection of sepsis is key to prevent its progression to severe sepsis and septic shock, which can cause organ failure and death. Diagnostic criteria for sepsis are nonspecific and hinder a timely diagnosis in patients. Therefore, there is currently a large effort to detect biomarkers that can aid physicians in the diagnosis and prognosis of sepsis. Mass spectrometry is often the method of choice to detect metabolomic and proteomic changes that occur during sepsis progression. These "omics" strategies allow for untargeted profiling of thousands of metabolites and proteins from human biological samples obtained from septic patients. Differential expression of or modifications to these metabolites and proteins can provide a more reliable source of diagnostic biomarkers for sepsis. Here, we focus on the current knowledge of biomarkers of sepsis and discuss the various mass spectrometric technologies used in their detection. We consider studies of the metabolome and proteome and summarize information regarding potential biomarkers in both general and neonatal sepsis.

  18. Viewpoint on the current status of researches on sepsis

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    Zheng-guo WANG

    2012-11-01

    Full Text Available Sepsis is a common complication after severe trauma and burn, and also one of the main causes of death. Recently, although some new progresses were seen in antibiotic therapy, the mortality of sepsis is still on the rise, and the death rate as a result of sepsis is higher than a total of that of prostate cancer, breast cancer and AIDS. Therefore, sepsis has obviously become one of the serious ailments threatening human health. The present paper introduced the international definition of sepsis, severe sepsis and septic shock, the current researches on diagnosis and therapy, and proposed that we should not only pay attention to pathogenesis and treatment, but also to sepsis prevention in sepsis researches, and we should try to find out the breakthrough in the interaction and dynamic balance between human being and pathogenic factors. Researches on the strategies to revert strong toxicity of infectious agents to non-toxic or weak pathogenic factors, and to conduct further research concerning biological characteristics of microorganisms and mechanism of drug resistance in order to render them to lose the drug resistance ability, or to increase its sensitivity to the drugs. The above suggested approaches might form the future strategies for preventing and controlling sepsis.

  19. Haemophilus influenzae: a forgotten cause of neonatal sepsis?

    Science.gov (United States)

    Dobbelaere, A; Jeannin, P; Bovyn, T; Ide, L

    2015-06-01

    Due to the introduction of the conjugate vaccine against serotype b, neonatal sepsis caused by Haemophilus influenzae became very rare. There is little data in Belgium concerning the prevalence of H. influenzae early onset neonatal sepsis and articles about neonatal sepsis and H. influenzae published in the last decade are scarce. We report two invasive infections with a non-typeable H. influenzae. These cases show that neonatal sepsis caused by non-typeable H. influenzae may be underestimated and we believe that there is need for a better registration of this kind of infection.

  20. Positive maternal C-reactive protein predicts neonatal sepsis.

    Science.gov (United States)

    Jeon, Ji Hyun; Namgung, Ran; Park, Min Soo; Park, Koo In; Lee, Chul

    2014-01-01

    To evaluate the diagnostic performance of maternal inflammatory marker: C-reactive protein (CRP) in predicting early onset neonatal sepsis (that occurring within 72 hours after birth). 126 low birth weight newborns (gestation 32±3.2 wk, birth weight 1887±623 g) and their mothers were included. Neonates were divided into sepsis group (n=51) including both proven (positive blood culture) and suspected (negative blood culture but with more than 3 abnormal clinical signs), and controls (n=75). Mothers were subgrouped into CRP positive ≥1.22 mg/dL (n=48) and CRP negative neonatal sepsis according to maternal condition. Maternal CRP was significantly higher in neonatal sepsis group than in control (3.55±2.69 vs. 0.48±0.31 mg/dL, p=0.0001). Maternal CRP (cutoff value >1.22 mg/dL) had sensitivity 71% and specificity 84% for predicting neonatal sepsis. Maternal CRP positive group had more neonatal sepsis than CRP negative group (71% vs. 29%, pneonatal sepsis in maternal CRP positive group versus CRP negative group was 10.68 (95% confidence interval: 4.313-26.428, pneonatal sepsis significantly increased in the case of positive maternal CRP (≥1.22 mg/dL). In newborn of CRP positive mother, the clinician may be alerted to earlier evaluation for possible neonatal infection prior to development of sepsis.

  1. Bacteriological profile and clinical predictors of ESBL neonatal sepsis.

    Science.gov (United States)

    Sharma, Deepak; Kumar, Chetan; Pandita, Aakash; Pratap, Oleti Tejo; Dasi, Teena; Murki, Srinivas

    2016-01-01

    Bacteriologic profile and risk factors for ESBL sepsis in newborns admitted to a Level III NICU. This was a retrospective observational study that enrolled newborns admitted to NICU with perinatal risk factors or clinical signs of sepsis and positive blood culture from January 2013 to August 2014. Blood cultures were done by BACTEC and ESBL production was evaluated from double-disc synergy method. Maternal, perinatal and neonatal risk factors were recorded from the case records and computerized information base. Mothers received cephalosporins for PPROM but its use was restricted in newborns for both probable and culture-positive sepsis. Among the infants with sepsis 24% had early-onset sepsis. The incidence of ESBL of early-onset Gram-negative sepsis (EOGNS) was 44.7% (n = 17 of 38) and it was 65% in late-onset Gram-negative sepsis (n = 84 of 129). The predominant ESBL-producing microbe responsible for neonatal sepsis was Klebsiella sp. Among newborns with EOGNS, the risk factors for the production of ESBL were preterm PROM (p = 0.004) and maternal exposure to antibiotics (p = 0.05). ESBL Gram-negative sepsis is a substantial problem in neonatal infections. Maternal exposure to cephalosporins and maternal PPROM are important risk factors for ESBL Gram-negative EOS.

  2. Sepsis neonatal cervicomaxilofacial (1996 a 2005 Neonatal cervicomaxillofacial sepsis (1996-2005

    Directory of Open Access Journals (Sweden)

    Zoila del S. López Díaz

    2007-12-01

    Full Text Available Se realiza un estudio retrospectivo y longitudinal de la sepsis cervicomaxilofacial en los neonatos ingresados en nuestra unidad de cuidados intensivos en un período de 10 años. Encontramos una incidencia promedio de 1,20 por cada 100 ingresos, y el predominio del grupo de edades entre 7 y 27 días de vida (sepsis tardía, del sexo femenino y del color blanco de la piel. La celulitis facial fue ocasionada por trauma obstétrico y fue el diagnóstico más frecuente. No encontramos relación entre la presencia de sepsis y la edad gestacional, el conteo de Apgar o el peso al nacer, pues en el mayor número de niños estos resultados estuvieron dentro de límites normales. El tratamiento más utilizado fue la antibioticoterapia con asociación de 2 o más antibióticos, y entre estas la más socorrida fue la asociación de penicilina y gentamicina. Cuando la sepsis tuvo una repercusión sistémica muy grave, se utilizó además inmunoglobulinoterapia. La evolución fue satisfactoria en el 100 % de los casos, la mayoría de los cuales necesitó internación hospitalaria hasta los 7 días. No hubo fallecidos.A retrospective and longitudinal study of cervicomaxillofacial sepsis in the neonates admitted in our intensive care unit in a period of 10 years was conducted. An average incidence of 1.20 per 100 admissions, as well as the predominance of white female infants aged 7-27 days old (late sepsis were observed. Facial cellulitis was caused by obstetric trauma and it was the most frequent diagnosis. No relation between the presence of sepsis and gestational age, Apgar score, or birth weight, was found, since in most of the children these results were within the normal limits. The most used treatment was the antibiotic therapy with the association of 2 or more antibiotics. The combination of penicillin and gentamicin was the most common treatment. In those cases, among whom the sepsis had a very severe systemic repercussion, immunoglobulin therapy was

  3. Diagnosis of post-traumatic sepsis according to "Sepsis guidelines": a cross-sectional survey of sepsis in a trauma intensive care unit

    Directory of Open Access Journals (Sweden)

    Hao TANG

    2016-04-01

    Full Text Available Objective  To investigate the prevalence and risk factors of post-traumatic sepsis, and to evaluate the rationality of the 1992, 2001 and 2012 international sepsis definitions in diagnosing post-traumatic sepsis in a trauma intensive care unit (ICU in China. Methods  A one-day cross-sectional survey of trauma patients who met the inclusion criteria was conducted from 8:00 a.m., June 16, 2014 to 8:00 a.m., June 17, 2014 in the trauma ICU of Daping Hospital. The survey data included demographic information, clinical characteristics, pertinent scores (APACHE Ⅱ, SOFA, GCS, ISS and injury mechanism. According to the definition of sepsis as depicted in the 1992, 2001, and 2012 "International Guideline of Sepsis", the patients were divided into A, B and C groups. The infection site, infection pathogens, and key medical treatment were recorded, the infection identified, and the 28day mortality recorded. A positive pathogen culture of respiratory and urinary tracts, blood, cerebrospinal fluid, and wound secretion was adopted as the diagnostic "gold standard" for septic infection. The diagnostic sensitivity and specificity of the three versions of the guidelines were statistically analyzed and the diagnostic feasibility of each definition was assessed. Results  A total of 30 trauma patients were enrolled, twenty-three patients met the 1992 sepsis criteria, 22 met the 2001 criteria, and 20 met the 2012 criteria. The prevalence rates were 76.7%, 73.3%, and 66.7%, respectively, and there was no significant statistical difference. Four patients died within 28 days, which was in line with the diagnostic criteria of the three versions of the sepsis criteria. The 28-day mortality in the three sepsis guidelines groups was 17.4%, 18.2%, and 25.0%, respectively, indicating no statistical difference. By adopting culture-positive pathogens as the "gold standard" of septic infection, the diagnostic sensitivity and specificity of the group A was 77.8% and 25

  4. DIAGNOSTICS AND TREATMENT OF THE SEPSIS AND SEPTIC SHOCK IN CHILDREN

    Directory of Open Access Journals (Sweden)

    R.F. Tepaev

    2010-01-01

    Full Text Available Sepsis is one of the leading causes of mortality in children. Timely diagnosis is the most important condition of successful therapy for sepsis. The work provides modern recommendations for diagnosis of the systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, sets out key guidelines for administering and treating severe sepsis and septic shock in children. Key words: systemic inflammatory response syndrome, sepsis, septic shock, children. (Pediatric Pharmacology. – 2010; 7(5:24-29

  5. Systematic Review of Gender Differences in Sepsis Management and Outcomes.

    Science.gov (United States)

    Failla, Kim Reina; Connelly, Cynthia D

    2017-05-01

    Contributors to disparities in sepsis management have been attributed to genetic susceptibility, differences in clinical presentation, and healthcare delivery. The influence of gender on survival or mortality of patients with sepsis-related diagnoses is unclear. The purpose of the current study was to systematically review published research to identify factors and outcomes associated with sepsis management and outcomes based on gender differences. Covering a period from 2006 to 2016, a literature search was conducted on four electronic data bases including the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EBSCO, MedlinePlus, and PubMed. Content analysis of each article was performed independently by two authors. The guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was the method used to assess the quality of evidence of the articles in this review. A full review was completed on a total of 452 identified potentially relevant publications, and 7 publications met inclusion criteria. The methodological approaches included prospective and retrospective observational studies, and prospective and historical cohort studies. The aim of these studies was to identify if gender differences exist related to sepsis-related mortality, completion of Surviving Sepsis Campaign resuscitation bundle elements, sepsis-related care processes, and sepsis-related incidence and source. Clinical sepsis studies evaluating gender and sepsis-related management and mortality are inconclusive and complex. Three different outcomes exist: no difference, higher risk in females, or higher risk in males. Further studies are needed to support the presence of gender disparities on sepsis-related healthcare outcomes. Providers should understand the importance of adhering to sepsis protocols and minimizing treatment disparities including gender differences. © 2017 Sigma Theta Tau International.

  6. Using the integrated nurse leadership program to reduce sepsis mortality.

    Science.gov (United States)

    Kliger, Julie; Singer, Sara J; Hoffman, Frank H

    2015-06-01

    The Integrated Nurse Leadership Program (INLP) is a collaborative improvement model focused on developing practical leadership skills of nurses and other frontline clinicians to lead quality improvement efforts. Sepsis is a major challenge to treat because it arises unpredictably and can progress rapidly. Nine San Francisco Bay Area hospitals participated in a 22-month INLP Sepsis Mortality Reduction Project to improve sepsis detection and management. The INLP focused on developing leadership and process improvement skills of nurses and other frontline clinicians. Teams of trained clinicians then implemented three strategies to improve early identification and timely treatment of sepsis: (1) sepsis screening of all patients, with diagnostic testing according to protocol; (2) timely treatment on the basis of key elements of Early Goal-Directed Therapy (EGDT); and (3) ongoing data review. Each hospital agreed to pursue the goal of reducing sepsis mortality by 15% by the end of the project. In the data collection period (baseline, July-December 2008 and project completion, January-June 2011), team members showed strong improvement in perceived leadership skills, team effectiveness, and ability to improve care quality. During this period, sepsis mortality for eight of the participating hospitals (Hospital 9 joined the project six months after it began) decreased by 43.7%-from 28% in the baseline period to 16% at project completion. Sepsis mortality rates trended downward for all hospitals, significantly decreasing (pone hospital, pmanagement of septic patients, hospitals participating in the INLP Sepsis Mortality Reduction Project achieved reductions in sepsis mortality during the study period and sustained reductions for more than one year later. The INLP model can be readily applied beyond sepsis management and mortality to other quality problems.

  7. Diagnostic and prognostic utility of tissue factor for severe sepsis and sepsis-induced acute lung injury.

    Science.gov (United States)

    Xue, Mingming; Sun, Zhan; Shao, Mian; Yin, Jun; Deng, Zhi; Zhang, Jin; Xing, Lingyu; Yang, Xiaoliang; Chen, Bin; Dong, Zhimin; Han, Yi; Sun, Si; Wang, Yuxin; Yao, Chenling; Chu, Xun; Tong, Chaoyang; Song, Zhenju

    2015-05-30

    Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) play a central role in the endothelial permeability regulation and dysfunction, which is associated with the development of sepsis and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The aim of this study is to assess the diagnostic and prognostic values of TF and TFPI in patients with sepsis and sepsis-induced ARDS. A total of 62 patients with sepsis, 167 patients with severe sepsis and 32 healthy volunteers were enrolled in this prospective observational study. TF and TFPI levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients with sepsis-induced ARDS showed significantly higher median levels of TF compared with patients without ARDS (1425.5 (1019.9 to 2595.2) pg/ml vs 916.2 (724.1 to 1618.2) pg/ml, P 0.05). The AUC of TF for the diagnosis of sepsis-induced ARDS was 0.749 (95% confidence interval (CI) 0.675-0.822). Plasma TF levels in the non-survivors of severe sepsis were significantly higher than those of survivors (1618.6 (1017.1 to 2900.8) pg/ml vs. 979.9 (757.2 to 1645.5) pg/ml, P 0.05). Our data showed that tissue factor is a valuable diagnostic biomarker for the diagnosis of sepsis-induced ARDS. Moreover, tissue factor is a strong prognostic marker for short-term mortality in severe sepsis and sepsis-induced ARDS patients.

  8. Disseminated intravascular coagulation in meningococcal sepsis. Case 7

    NARCIS (Netherlands)

    Zeerleder, S.; Zürcher Zenklusen, R.; Hack, C. E.; Wuillemin, W. A.

    2003-01-01

    We report on a man (age: 49 years), who died from severe meningococcal sepsis with disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome and extended skin necrosis. We discuss in detail the pathophysiology of the activation of coagulation and fibrinolysis during sepsis.

  9. Treatment of neonatal sepsis with intravenous immune globulin

    DEFF Research Database (Denmark)

    Brocklehurst, Peter; Farrell, Barbara; King, Andrew

    2011-01-01

    Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...

  10. Neonatal sepsis: Highlighting the principles of diagnosis and ...

    African Journals Online (AJOL)

    Neonatal sepsis is a clinical syndrome consisting of nonspecific symptoms and signs of infection, accompanied by a bacteraemia in the first 28 days of life. The risk of neonatal sepsis and death increases with decreasing birth weight and gestational age. South African data have reported the overall incidence of neonatal ...

  11. Prevention of wound sepsis in amputations by peri-operative ...

    African Journals Online (AJOL)

    as regards development of sepsis in wounds closed primarily or left open while under A-CA cover. In a series of 44 patients with lower limb ischaemia requiring amputation for major limb sepsis, the per- formance of a new antibiotic combination with B- lactamase-inhibiting properties, amoxycillin plus . c1avulanic acid ...

  12. Serum procalcitonin as an early marker of neonatal sepsis | Ballot ...

    African Journals Online (AJOL)

    Background. It has recently been suggested that procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. This study was to evaluate the role of PCT as a single early marker of neonatal sepsis. Setting. Neonatal Unit, Johannesburg Hospital, and Microbiology Laboratory, National Health ...

  13. Trends in profiles of bacteria causing neonatal sepsis in Central ...

    African Journals Online (AJOL)

    Developing countries suffer from a huge burden of neonatal sepsis. Neonatal mortality and long term sequelae or morbidity portends huge costs for the poor Nigerian economy. We identified trends in bacterial agents implicated in neonatal sepsis and their antibiotic susceptibility profiles at the National Hospital Abuja over ...

  14. MicroRNA's are novel biomarkers in sepsis

    DEFF Research Database (Denmark)

    Søndergaard, Edith Smed; Alamili, Mahdi; Coskun, Mehmet

    2015-01-01

    between differential expression of miRs and sepsis. Methods: We performed a systematic search in the MEDLINE, Embase and Cochrane Library databases according to PRISMA-guidelines. We included all original English-language studies including human subjects admitted to the ICU with sepsis or systemic...

  15. Sepsis-induced immunoparalysis: mechanisms, markers, and treatment options

    NARCIS (Netherlands)

    Hamers, L.A.C.; Kox, M.; Pickkers, P.

    2015-01-01

    Sepsis remains the leading cause of death in the ICU. Considering the key role of the immune system in sepsis, immunomodulation represents an attractive target for adjunctive therapy. Until recently, clinical trials focused on suppression of the immune system, but this approach failed to improve

  16. Early diagnostic method for sepsis based on neutrophil MR imaging

    Directory of Open Access Journals (Sweden)

    Shanhua Han

    2015-06-01

    Conclusion: Mouse and human neutrophils could be more effectively labelled by Mannan-coated SPION in vitro than Feridex. Sepsis analog neutrophils labelled by Mannan-coated SPIONs could be efficiently detected on MR images, which may serve as an early diagnostic method for sepsis.

  17. Diagnosis trajectories of prior multi-morbidity predict sepsis mortality

    DEFF Research Database (Denmark)

    Beck, Mette Kristina; Jensen, Anders Boeck; Nielsen, Annelaura Bach

    2016-01-01

    Sepsis affects millions of people every year, many of whom will die. In contrast to current survival prediction models for sepsis patients that primarily are based on data from within-admission clinical measurements (e.g. vital parameters and blood values), we aim for using the full disease histo...

  18. [Clinical statistical study on puerperal sepsis risk factors].

    Science.gov (United States)

    Dimitriu, Gabriela

    2010-01-01

    The aim of this study was to assess some risk factors involved in puerperal sepsis, such as: cesarean delivery, diabetes mellitus, preterm delivery and obesity, history of infections and anemia. The authors highlighted that new prevention methods and techniques could reduce the incidence and severity of post-cesarean puerperal sepsis (uterine infarction, peritonitis, toxic shock syndrome with Group A streptococcus).

  19. Quality in practice: preventing and managing neonatal sepsis in Nicaragua.

    Science.gov (United States)

    López, Sergio; Wong, Yudy; Urbina, Luis; Gómez, Ivonne; Escobar, Flavia; Tinoco, Bernarda; Parrales, Alba

    2013-10-01

    Incorrect and excessive diagnosis of newborn infections in Nicaragua caused overcrowding in the neonatal intensive care units and unnecessary hospitalization. A baseline study in nine hospitals found that none correctly utilized disinfectants, sterilization or hand hygiene and that diagnosis of neonatal sepsis was based primarily on clinical manifestations. In 2007, the Ministry of Health (MINSA), with Unites States Agency for the International Development technical assistance, began developing guidelines and implementing quality improvement in infection prevention and control to reduce neonatal infections. In a second intervention phase, the MINSA introduced an algorithm for correct identification of maternal risk factors and standardized laboratory tests for neonatal sepsis. Interventions included developing national guidelines on correct use of disinfectants and hand hygiene; training medical staff on the guidelines; revising the basic medical supply list to support appropriate antisepsis; defining a package of diagnostic tests for neonatal sepsis and systematically measuring compliance with the new procedures. The 18 hospitals achieved appropriate use of disinfectants in a 12-month period. In seven hospitals that introduced improvements in diagnosis and management of neonatal sepsis, application of the standardized laboratory package in suspected sepsis cases increased from 0% in April 2009 to 93% in July 2011, and the median incidence of neonatal sepsis was reduced by 67%. The organizational changes implemented for the diagnosis and verification of neonatal sepsis led to a reduction in the newborn sepsis admissions and expenditures for antibiotics, allowing resources to be redirected to treating other critically ill newborns.

  20. Impact of Socioeconomic Factors on Neonatal Sepsis in Jos, Nigeria ...

    African Journals Online (AJOL)

    The most common isolates were Klebsiella pneumonia, Staphylococcus aureus and Escherichia coli. Delivery at home had the highest percentage of culture proven sepsis (52.2%). Mothers with no formal education and those with only primary education also had high proportions of culture proven sepsis (41.1% and 58.8% ...

  1. [Evaluation of coagulation disorders with thrombelastography in patients with sepsis].

    Science.gov (United States)

    Zhong, Shengjian; Zhang, Chunbao; Hu, Juntao; Tang, Zhanhong

    2016-02-01

    To compare the results of thrombelastography (TEG) and the conventional coagulability test in patients with sepsis, and to discuss the value of TEG in monitoring blood coagulation dysfunction in patients with sepsis. The clinical data of 92 adult patients with sepsis admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The patients were divided into sequential organ failure assessment (SOFA) score ≥ 12 group (n = 47) and SOFA coagulation function served as control group. The venous blood was collected for conventional blood coagulation test and routine examination of blood, D-dimer, procalcitonin (PCT), and TEG, and the differences were compared among three groups. Correlations between SOFA and various indexes of patients with sepsis were analyzed by Spearman rank correlation method. As shown in the results of the conventional blood coagulation test, D-dimer was gradually increased with the aggravation of the disease, the values in non-sepsis, SOFA coagulation test might not respond quickly to the change in coagulation status of sepsis patients. As shown in the results of TEG, the values of reaction time (R value) and kinetics time (K value) in SOFA 0.05; K value (minutes): 4.2 (3.4, 7.1) vs. 1.5 (1.3, 1.8), P coagulation index (CI) in SOFA coagulation in patients with sepsis, and distinguish the hypercoagulable and hypocoagulable state. TEG may be a valuable tool to evaluate degree and risk of sepsis objectively.

  2. Biomarkers of Endothelial Cell Activation in Early Sepsis

    DEFF Research Database (Denmark)

    Skibsted, Simon; Jones, Alan E; Puskarich, Michael A

    2013-01-01

    molecule 1, and plasminogen activator inhibitor 1 (PAI-1). Outcomes were organ dysfunction and in-hospital mortality. RESULTS: We enrolled a total of 166 patients: 63 with sepsis (38%), 61 with severe sepsis (37%), and 42 with septic shock (25%). All endothelial biomarkers were significantly associated...

  3. Letter to editor Platelet volume evaluation in patients with sepsis ...

    African Journals Online (AJOL)

    I have read the article published by Guclu et al. with a great interest.1 They examined platelet indices in patients with sepsis. Mean platelet volume (MPV) and platelet distribution width (PDW) were significantly higher in patients with sepsis than in controls. MPV and PDW were significantly higher in patients with severe ...

  4. Prevalence and factors associated with neonatal sepsis among ...

    African Journals Online (AJOL)

    TOSHIBA

    Clinical features were used for diagnosing neonatal sepsis. Using predator confirmed from previous study a child who showed the following symptoms: bradycardia, seizures/convulsion, fever, apnoea, reduced sucking, reduced movements, vomiting and infected umbilical cord was classified as a child with sepsis (English ...

  5. Sepsis: at-risk patients, clinical manifestations and management

    African Journals Online (AJOL)

    Sepsis is a major clinical challenge, especially to clinicians working in emergency and critical care units. Research over the last decade into a better understanding of the pathophysiology and management of sepsis has resulted in a remarkable increase of new knowledge on the subject. Some findings translate into ...

  6. [Predictive value of procalcitonin in children with suspected sepsis].

    Science.gov (United States)

    Bustos B, Raúl; Padilla P, Oslando

    2015-01-01

    The use of biomarkers could be a tool for diagnosis, prognosis and stratifying children with sepsis. Our main goal was to analyze the value of procalcitonin (PCT), C reactive protein (CRP) and lactate in predicting mortality, septic shock and the stratification in children with suspected sepsis Prospective study in 81 patients. Plasma levels of PCT, CRP and lactate were measured at admission in the pediatric intensive care unit. Patients were categorized into systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock. Concentrations of PCT (ng/mL) increased significantly according to the severity of sepsis: 0.36 (0-1.2) for systemic inflammatory response syndrome; 1.96 (0.4-3.5) for sepsis; 7.5 (3.9-11.1) for severe sepsis; and 58.9 (35.1-82.7) for septic shock (P<.001). Compared to CRP and lactate, the area under the ROC curve revealed a good discriminative power of PCT to predict septic shock and mortality, 0.91 (95% CI: 0.83-0.97) and 0.80 (95% CI: 0.69-0.88), respectively. In contrast to CRP and lactate, the determination of PCT in pediatric intensive care unit admission is a good predictor of mortality and septic shock and can stratify patients according to severity of sepsis. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Risk factors, host response and outcome of hypothermic sepsis

    NARCIS (Netherlands)

    Wiewel, Maryse A; Harmon, Matthew B; van Vught, Lonneke A; Scicluna, Brendon P; Hoogendijk, Arie J; Horn, Janneke; Zwinderman, Aeilko H; Cremer, Olaf L; Bonten, Marc J; Schultz, Marcus J; van der Poll, Tom; Juffermans, Nicole P; Wiersinga, W Joost

    2016-01-01

    BACKGROUND: Hypothermia is associated with adverse outcome in patients with sepsis. The objective of this study was to characterize the host immune response in patients with hypothermic sepsis in order to determine if an excessive anti-inflammatory response could explain immunosuppression and

  8. Diagnosis of Sepsis in Critically Ill Patients

    Directory of Open Access Journals (Sweden)

    M. L. Romasheva

    2007-01-01

    Full Text Available Objective: to ascertain the informative value of determining procalcitonin in the diagnosis of critical conditions and in the evaluation of the efficiency of performed therapy.Subjects and methods. Sixty patients aged 25—50 years (38.1±11.2 years who had signs of the systemic inflammatory reaction syndrome, including 30 (50.0% patients with severe sepsis, 21 (35.0% with septic shock, 3 (5.0% with meningitis of varying etiology, 2 (3.3% with Candida infection, and 1 (1.7% with vasculitis, and 3 (5.0% with pulmonary thromboembolism, were examined. In all the patients, serum procalcitonin was determined by an RCTv-Q test (BRAHMS in the first 24 hours of stay in an intensive care unit (ICU and 72 hours after the initiation of multicomponent therapy.Results. Patients with severe sepsis and multiple organ dysfunction has a positive test with a plasma procalcitonin level of 2 ng/ml or higher in 100% of cases. In meningitis, the concentration of procalcitonin was 0.5 to 2 ng/ml; in Candida infection and thrombovasculi-tis, that was as high as 0.5 ng/ml. A negative test was obtained in pulmonary thromboembolism. Extracorporeal treatments (continuous venovenous hemodiafiltration on a PRISMA apparatus were used as part of complex therapy in 14 patients with septic shock and multiple organ dysfunctions. In 9 (64.3% of them, its concentration decreased to a varying degree, blood acid-base balance became normal, vital functions stabilized; 5 (13.5% died.Conclusion. Procalcitonin is a highly specific marker of sepsis. In patients with severe sepsis, lower procalcitonin concentrations and septic shock suggests the efficiency of the performed therapy in this category of patients. Procalcitonin may be recognized to be a reliable parameter of the monitoring of not only the severity of bacterial infection, but also the evaluation of the efficiency of treatment in critically ill patients in an ICU. 

  9. Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children.

    Science.gov (United States)

    Spanaki, Anna Maria; Tavladaki, Theonymfi; Dimitriou, Helen; Kozlov, Andrey V; Duvigneau, J Catharina; Meleti, Eftychia; Weidinger, Adelheid; Papakonstantinou, Evangelos; Briassoulis, George

    2018-01-16

    Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX. Resistin, eHSP72, eHSP90α, and nitrate were longitudinally higher in sepsis compared with SIRS (pmetabolic pattern were repressed in sepsis compared with SIRS (pmetabolism, mHSP72, and induced resistin and adiponectin (pmetabolic-hormones and eHSP72/HSP90α, repression of bioenergetics and innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased resistin and adiponectin are associated with poor outcome. © 2018 American Society for Parenteral and Enteral Nutrition.

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

    Science.gov (United States)

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

    2014-01-01

    Sepsis — severe 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

  11. [Usefulness of Procalcitonin Measurement for the Detection of Sepsis].

    Science.gov (United States)

    Toh, Hiromi; Harada, Sadako; Kakudou, Tomoko; Era, Fumiyoshi; Tokushige, Chiemi; Yoshimura, Hisae; Kawashima, Hironobu; Ohkubo, Kumiko; Ishikura, Hiroyasu; Matsunaga, Akira

    2014-10-01

    Procalcitonin (PCT) is a frequently used marker for bacterial sepsis. The present study was aimed to assess the usefulness of PCT measurement in patient with sepsis. We studied the relationship between serum PCT level and blood culture in clinical 209 cases admitted from January 2010 through June 2010. We compared PCT level with blood culture results and other clinical data, and diagnosis such as sepsis and systemic inflammatory response syndrome (SIRS) were obtained from the medical records. In the case of patients with positive blood cultures and PCT sepsis. The PCT measurement could be performed and reported rapidly and provided valuable information before availability of culture results. In this study, we found that the PCT would be a useful biomarker for confirming and ruling out sepsis.

  12. Role of pore-forming toxins in neonatal sepsis.

    Science.gov (United States)

    Sonnen, Andreas F-P; Henneke, Philipp

    2013-01-01

    Protein toxins are important virulence factors contributing to neonatal sepsis. The major pathogens of neonatal sepsis, group B Streptococci, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus, secrete toxins of different molecular nature, which are key for defining the disease. Amongst these toxins are pore-forming exotoxins that are expressed as soluble monomers prior to engagement of the target cell membrane with subsequent formation of an aqueous membrane pore. Membrane pore formation is not only a means for immediate lysis of the targeted cell but also a general mechanism that contributes to penetration of epithelial barriers and evasion of the immune system, thus creating survival niches for the pathogens. Pore-forming toxins, however, can also contribute to the induction of inflammation and hence to the manifestation of sepsis. Clearly, pore-forming toxins are not the sole factors that drive sepsis progression, but they often act in concert with other bacterial effectors, especially in the initial stages of neonatal sepsis manifestation.

  13. How Can the Microbiologist Help in Diagnosing Neonatal Sepsis?

    Directory of Open Access Journals (Sweden)

    Michela Paolucci

    2012-01-01

    Full Text Available Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis—EONS or later (late-onset neonatal sepsis—LONS. These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis.

  14. Elucidating the role of genomics in neonatal sepsis.

    Science.gov (United States)

    Srinivasan, Lakshmi; Kirpalani, Haresh; Cotten, Charles Michael

    2015-12-01

    Sepsis is a major cause of neonatal morbidity and mortality, especially in vulnerable preterm populations. Immature immune defenses, and environmental and maternal factors contribute to this risk, with as many as a third of very preterm infants experiencing sepsis during their stay in the neonatal intensive care unit (NICU). Epidemiologic and twin studies have suggested that there is a genetic contribution to sepsis predilection. Several investigators have conducted candidate gene association studies on variants of specific interest and potential functional significance in neonatal sepsis. In this review, we describe details of studies that have evaluated genetic susceptibility in neonatal sepsis, and summarize findings from a review of candidate gene association studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. How Can the Microbiologist Help in Diagnosing Neonatal Sepsis?

    Science.gov (United States)

    Paolucci, Michela; Landini, Maria Paola; Sambri, Vittorio

    2012-01-01

    Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis—EONS) or later (late-onset neonatal sepsis—LONS). These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis. PMID:22319539

  16. The new normal: immunomodulatory agents against sepsis immune suppression.

    Science.gov (United States)

    Hutchins, Noelle A; Unsinger, Jacqueline; Hotchkiss, Richard S; Ayala, Alfred

    2014-04-01

    Sepsis is the leading cause of death among critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the proinflammatory stage have failed clinically; therefore, new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis models and patient samples suggest that cytokines such as interleukin-7 (IL-7), IL-15, granulocyte macrophage colony-stimulating factor (GM-CSF), as well as co-inhibitory molecule blockade, such as anti-programmed cell death receptor-1 (anti-PD-1) and anti-B and T lymphocyte attenuator (anti-BTLA), may have utility in alleviating the clinical morbidity associated with sustained sepsis. This review discusses some of these novel immunomodulatory agents and evaluates their potential use as therapeutics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Early management of severe sepsis: concepts and controversies.

    Science.gov (United States)

    Marik, Paul E

    2014-06-01

    Sepsis is among the most common reasons for admission to ICUs throughout the world, and it is believed to be the third most common cause of death in the United States. The pathogenetic mechanism and physiologic changes associated with sepsis are exceedingly complex, but our understanding is evolving rapidly. The major pathophysiologic changes in patients with septic shock include vasoplegic shock (distributive shock), myocardial depression, altered microvascular flow, and a diffuse endothelial injury. These pathophysiologic changes play a central role in the management of sepsis. The early management of patients with severe sepsis and septic shock centers on the administration of antibiotics, IV fluids, and vasoactive agents, followed by source control. However, the specific approach to the resuscitation of patients with septic shock remains highly controversial. This review provides a practical and physiologic-based approach to the early management of sepsis and explores the controversies surrounding the management of this complex condition.

  18. [Before-after study of the effect of implementing a sepsis code for emergency departments in the community of Aragon].

    Science.gov (United States)

    Ferreras Amez, José María; Arribas Entrala, Belén; Sarrat Torres, Marco Antonio; García Noain, Alberto; Caudevilla Martínez, Aranzazu; Colás Oros, Carlos; Aladrén Pérez, Belén; Rodero Álvarez, Fernando

    2017-06-01

    To study the effect of an emergency department sepsis code on the degree of compliance with measures recommended by the Surviving Sepsis Campaign and short-term mortality in the Spanish Autonomous Community of Aragon. Quasi-experimental study of 2 case cohorts, one including of cases before implementation of the sepsis code and one included cases managed afterwards. We extracted retrospectively data from hospital records for infectious processes and organ failures between December 2012 and January 2013 for the pre-code group and between December 2014 and January 2015 for the post-code group. Staff training sessions on the campaign recommendations were provided and the code, which specified clinical pathways, was activated electronically on inputting clinical variables at the moment of triage. Outcome measures were the percentage of compliance with the campaign's recommendations in the first 3 hours after a patient's arrival at the emergency department in-hospital mortality, and 30-day mortality. A total of 222 cases were included in each group. Compliance with the following campaign recommendations improved after implementation of the sepsis code: antibiotic therapy in the first hour (P=.100), extractions for blood cultures (P 001), lactic acid measurement (P 001), and recommended fluid loading (P 001). In-hospital mortality was 31.1% in the pre-code cohort and 20.7% post-code; 30-day mortality rates were 30.1% and 19.8%, respectively (P=.016, all comparisons). Use of a sepsis code led to short-term improvement in how often the measures recommended by a sepsis survival campaign were put into practice.

  19. Intestinal radiation syndrome: sepsis and endotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

    1985-03-01

    Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and /sup 137/Cs ..gamma.. rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and ..gamma..-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presence of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome.

  20. Does Dexamethasone Helps in Meningococcal Sepsis?

    Science.gov (United States)

    Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

    2017-06-01

    Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease.

  1. Mechanisms of Enhanced Lung Injury during Sepsis

    Science.gov (United States)

    Czermak, Boris J.; Breckwoldt, Maren; Ravage, Zachary B.; Huber-Lang, Markus; Schmal, Hagen; Bless, Nicolas M.; Friedl, Hans P.; Ward, Peter A.

    1999-01-01

    A major complication in sepsis is progressively impaired lung function and susceptibility to intrapulmonary infection. Why sepsis predisposes the lung to injury is not clear. In the current studies, rats were rendered septic by cecal ligation/puncture and evaluated for increased susceptibility to injury after a direct pulmonary insult (deposition of IgG immune complexes or airway instillation of lipopolysaccharide). By itself, cecal ligation/puncture did not produce evidence of lung injury. However, after a direct pulmonary insult, lung injury in septic animals was significantly enhanced. Enhanced lung injury was associated with increased accumulation of neutrophils in lung, enhanced production of CXC chemokines (but not tumor necrosis factor-α) in bronchoalveolar lavage fluids, and increased expression of lung vascular intercellular adhesion molecule-1 (ICAM-1). Complement depletion or treatment with anti-C5a abolished all evidence of enhanced lung injury in septic animals. When stimulated in vitro, bronchoalveolar lavage macrophages from septic animals had greatly enhanced CXC chemokine responses as compared with macrophages from sham-operated animals or from septic animals that had been complement depleted. These data indicate that the septic state causes priming of lung macrophages and suggest that enhanced lung injury in the septic state is complement dependent and related to increased production of CXC chemokines. PMID:10233844

  2. Quick Sequential [Sepsis-Related] Organ Failure Assessment (qSOFA) and St. John Sepsis Surveillance Agent to Detect Patients at Risk of Sepsis: An Observational Cohort Study.

    Science.gov (United States)

    Amland, Robert C; Sutariya, Bharat B

    2017-02-01

    The 2016 Sepsis-3 guidelines included the Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) tool to identify patients at risk of sepsis. The objective was to compare the utility of qSOFA to the St. John Sepsis Surveillance Agent among patients with suspected infection. The primary outcomes were in-hospital mortality or admission to the intensive care unit. A multiple center observational cohort study design was used. The study population comprised 17 044 hospitalized patients between January and March 2016. For the primary analysis, receiver operator characteristic curves were constructed for patient outcomes using qSOFA and the St. John Sepsis Surveillance Agent, and the areas under the curve were compared against a baseline risk model. Time-to-event clinical process modeling also was applied. The St. John Sepsis Surveillance Agent, when compared to qSOFA, activated earlier and was more accurate in predicting patient outcomes; in this regard, qSOFA fell far behind on both objectives.

  3. Gene expression profiling of mononuclear cells from patients with sepsis secondary to community-acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Patricia Severino

    2014-12-01

    Full Text Available Mechanisms governing the inflammatory response during sepsis involve crosstalk between diverse signaling pathways, but current knowledge provides an incomplete picture of the syndrome. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis. In this study, we investigated whole-genome expression profiles in mononuclear cells from septic patients admitted in intensive care units with community-acquired pneumonia. Blood samples were collected at the time of sepsis diagnosis and seven days later since we aimed to evaluate the role of biological processes or genes possibly involved in patient recovery. Here we provide a detailed description of the study design, including clinical information, experimental methods and procedures regarding data analysis. Metadata corresponding to microarray results deposited in the database Gene Expression Omnibus (GEO under the accession number GSE48080 are also described in this report. Our dataset allows the identification of genes possibly associated with host defense to infection as well as gene expression patterns associated with patient outcome.

  4. [Significance of Toll-like receptors in the pathophysiology of surgical sepsis].

    LENUS (Irish Health Repository)

    Romics, Laszlo Jr

    2012-02-03

    The discovery of Toll-like receptors has substantially changed our knowledge of pathogen recognition. 11 Toll-like receptors have so far been described in humans. These recognize distinct pathogen associated molecular patterns, as well as endogenous ligands and small molecular synthetic compounds. TLRs have a multifunctional role in pathogen-triggered immune responses and represent an important connection between the "innate" and "adaptive" immunity. The role of the TLRs in the recognition of pathogens renders them a key figure in the activation of the immune response during surgical sepsis. However, emerging evidence points to a fundamental role in tumorigenesis, transplantation, wound healing, atherogenesis and inflammatory bowel disease. The aim hence was to review experimental data pertaining to the activation of TLR signalling pathways in conditions associated with surgical sepsis. A systematic review of the literature was undertaken by searching the MEDLINE database for the period 1966-2004 without language restriction. The paper also analyses the possible therapeutic utilization of the TLR signalling pathways in surgical sepsis.

  5. Neonatal CD71+ erythroid cells do not modify murine sepsis mortality

    Science.gov (United States)

    Wynn, James L.; Scumpia, Philip O.; Stocks, Blair T.; Romano-Keeler, Joann; Alrifai, Mhd Wael; Liu, Jin-Hua; Kim, Annette S.; Alford, Catherine E.; Matta, Pranathi; Weitkamp, Jörn-Hendrik; Moore, Daniel J.

    2015-01-01

    Sepsis is a major cause of neonatal mortality and morbidity worldwide. A recent report suggested murine neonatal host defense against infection could be compromised by immunosuppressive CD71+ erythroid splenocytes. We examined the impact of CD71+ erythroid splenocytes on murine neonatal mortality to endotoxin challenge or polymicrobial sepsis and characterized circulating CD71+ erythroid (CD235a+) cells in human neonates. Adoptive transfer or antibody-mediated reduction of neonatal CD71+ erythroid splenocytes did not alter murine neonatal survival to endotoxin challenge or polymicrobial sepsis challenge. Ex vivo immunosuppression of stimulated adult CD11b+ cells was not limited to neonatal splenocytes as it also occurred with adult and neonatal bone marrow. Animals treated with anti-CD71 antibody showed reduced splenic bacterial load following bacterial challenge compared to isotype-treated mice. However, adoptive transfer of enriched CD71+ erythroid splenocytes to CD71+-reduced animals did not reduce bacterial clearance. Human CD71+CD235a+ cells were common among cord blood mononuclear cells and were shown to be reticulocytes. In summary, a lack of effect on murine survival to polymicrobial sepsis following adoptive transfer or diminution of CD71+ erythroid splenocytes under these experimental conditions suggests the impact of these cells on neonatal infection risk and progression may be limited. An unanticipated immune priming effect of anti-CD71 antibody treatment was likely responsible for the reported enhanced bacterial clearance, rather than a reduction of immunosuppressive CD71+ erythroid splenocytes. In humans, the well-described rapid decrease in circulating reticulocytes after birth suggests they may have a limited role in reducing inflammation secondary to microbial colonization. PMID:26101326

  6. Using lean methodology to optimize time to antibiotic administration in patients with sepsis.

    Science.gov (United States)

    Brunsman, Allison C

    2018-03-01

    Results of a study to apply lean methodology to an inpatient pharmacy workflow to optimize timely administration of Centers for Medicare and Medicaid Services (CMS)-approved antibiotics for patients with severe sepsis or septic shock are presented. This quasi-experimental study was conducted at an 802-bed institution using lean methodology to assess the inpatient pharmacy workflow for dispensing antibiotics to adult patients. The preintervention and postintervention phases occurred from February to September, 2015, and from October 2015 to May 2016, respectively. Patients were included if they were hospitalized with an intensive care department 9 or 10 code for severe sepsis or septic shock, had an order for a CMS-approved antibiotic, and met clinical criteria for severe sepsis or septic shock. Patients were excluded if they received first-dose antibiotics in the emergency department. The primary outcome was time from CMS-approved antibiotic order entry to medication administration. Secondary outcomes included timeliness of individual workflow dispensing parameters, patient outcomes, and compliance with the newly implemented workflow. A total of 102 patients were included, 54 in the preintervention and 48 in the postintervention group. Baseline demographics between the groups were similar. There was a significant reduction in the median time from order entry to antibiotic administration by 40 minutes (preintervention phase 120 minutes versus postintervention phase 80 minutes, p = 0.014). Time from order verification to administration was significantly reduced. There was no difference in other secondary outcomes. Lean methodology was successfully used to reduce time to antibiotic administration, which led to improved compliance with the newly implemented sepsis CMS core measure. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  7. Serum procalcitonin levels in the postmortem diagnosis of sepsis.

    Science.gov (United States)

    Bode-Jänisch, S; Schütz, S; Schmidt, A; Tschernig, T; Debertin, A S; Fieguth, A; Hagemeier, L; Teske, J; Suerbaum, S; Klintschar, M; Bange, F C

    2013-03-10

    Procalcitonin is regarded as a valuable marker for sepsis in living persons and even in post-mortem investigations. At the Institute of Legal Medicine, 25 autopsy cases with suspected bacterial infectious diseases or sepsis were examined using the semi-quantitative PCT-Q(®)-test (B.R.A.H.M.S., Germany) in 2010 and 2011. As controls, 75 cadavers were used for which there was no suspicion of a bacterial infectious disease or sepsis. Femoral blood was cultured from the cases and from controls, and samples from the brain, heart, lungs, liver, spleen and kidneys were examined histologically for findings seen in sepsis. Twelve cases in the sepsis/infectious disease group (48%) were classifiable as sepsis following synopsis of PCT levels, autopsy results, and histopathological and microbiological findings. This study shows that the semi-quantitative PCT-Q(®)-test is a useful supplementary marker in routine autopsy investigations, capable of classifying death as due to sepsis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Importance of measuring lactate levels in children with sepsis.

    Science.gov (United States)

    Anil, Nisha

    2017-10-10

    Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  9. Telehealth Intensive Care Unit Nurse Surveillance of Sepsis.

    Science.gov (United States)

    Rincon, Teresa A; Manos, E LaVerne; Pierce, Janet D

    2017-09-01

    The purpose of this article is to describe the usability and human factors engineering standards used in development of a sepsis alert known as the sepsis prompt. Sensory processing, cognitive processing, signal detection, criterion response, and user satisfaction were evaluated with controlled user testing and critical incident response techniques. Nurses reported that the sepsis prompt was visible and distinct, making it easily detectable. The prompt provided a clear response mechanism and adequately balanced the number of false alerts with the likelihood of misses. Designers were able to use a mental model approach as they designed the prompt because the nurses were already using a manual sepsis detection process. This may have predisposed the nurses to response bias, and as such, they were willing to accommodate more false alarms than nurses who are not familiar with sepsis screening (surveillance). Nurses not currently screening for sepsis may not place the same value on this alert and find it an annoyance. The sepsis prompt met usability standards, and the nurses reported that it improved efficiency over the manual screening method.

  10. Risk Factors and Outcomes in Patients With Hypernatremia and Sepsis.

    Science.gov (United States)

    Ni, Hai-Bin; Hu, Xing-Xing; Huang, Xiao-Fei; Liu, Ke-Qin; Yu, Chen-Bin; Wang, Xiao-Meng; Ke, Lu

    2016-06-01

    Hypernatremia is an uncommon but important electrolyte abnormality in intensive care unit patients. Sepsis is one of the most common causes of intensive care unit admission, but few studies about the role of hypernatremia in sepsis has been published yet. In this study, we aimed to explore the risk factors for developing hypernatremia in patients with sepsis, and the prognosis of patients with sepsis with or without hypernatremia was also assessed. In this retrospective cohort study of 51 septic intensive care unit patients at a single center, we examined the risk factors for the development of hypernatremia and the association of hypernatremia with clinical outcomes using univariate and multivariable analyses. Clinical outcomes such as mortality and hospital duration of patients with or without hypernatremia were also compared. Acute Physiology and Chronic Health Evaluation II score (odds ratio = 1.15; 95% CI: 1.022-1.294) was found to be the only independent risk factor for hypernatremia in patients with sepsis. Moreover, patients developing hypernatremia during hospitalization showed significantly higher morbidity and mortality. Acute Physiology and Chronic Health Evaluation II score may be an independent risk factor for hypernatremia in patients with sepsis. Moreover, hypernatremia is strongly associated with worse outcome in sepsis. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  11. Circulating Endothelial Cells and Endothelial Progenitor Cells in Pediatric Sepsis.

    Science.gov (United States)

    Zahran, Asmaa Mohamad; Elsayh, Khalid Ibrahim; Mohamad, Ismail Lotfy; Hassan, Gamal Mohamad; Abdou, Madleen Adel A

    2016-03-01

    The aim of the study was to measure the number of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) in pediatric patients with sepsis and correlating it with the severity of the disease and its outcome. The study included 19 children with sepsis, 26 with complicated sepsis, and 30 healthy controls. The patients were investigated within 48 hours of pediatric intensive care unit admission together with flow cytometric detection of CECs and CEPs. The levels of both CECs and CEPs were significantly higher in patient with sepsis and complicated sepsis than the controls. The levels of CECs were higher in patients with complicated sepsis, whereas the levels of CEPs were lower in patients with complicated sepsis. Comparing the survival and nonsurvival septic patients, the levels of CEPs were significantly higher in the survival than in nonsurvival patients, whereas the levels of CECs were significantly lower in the survival than in nonsurvival patients. Serum albumin was higher in survival than in nonsurvival patients. Estimation of CECs and CEPs and their correlation with other parameters such as serum albumen could add important information regarding prognosis in septic pediatric patients.

  12. Construction and management of ARDS/sepsis registry with REDCap.

    Science.gov (United States)

    Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Li, Yimin; Zhang, Haibo

    2014-09-01

    The study aimed to construct and manage an acute respiratory distress syndrome (ARDS)/sepsis registry that can be used for data warehousing and clinical research. The workflow methodology and software solution of research electronic data capture (REDCap) was used to construct the ARDS/sepsis registry. Clinical data from ARDS and sepsis patients registered to the intensive care unit (ICU) of our hospital formed the registry. These data were converted to the electronic case report form (eCRF) format used in REDCap by trained medical staff. Data validation, quality control, and database management were conducted to ensure data integrity. The clinical data of 67 patients registered to the ICU between June 2013 and December 2013 were analyzed. Of the 67 patients, 45 (67.2%) were classified as sepsis, 14 (20.9%) as ARDS, and eight (11.9%) as sepsis-associated ARDS. The patients' information, comprising demographic characteristics, medical history, clinical interventions, daily assessment, clinical outcome, and follow-up data, was properly managed and safely stored in the ARDS/sepsis registry. Data efficiency was guaranteed by performing data collection and data entry twice weekly and every two weeks, respectively. The ARDS/sepsis database that we constructed and manage with REDCap in the ICU can provide a solid foundation for translational research on the clinical data of interest, and a model for development of other medical registries in the future.

  13. Challenges in the diagnosis and management of neonatal sepsis.

    Science.gov (United States)

    Zea-Vera, Alonso; Ochoa, Theresa J

    2015-02-01

    Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Although recent medical advances have improved neonatal care, many challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. 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?

  15. 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

  16. Colloids in sepsis: evenly distributed molecules surrounded by uneven questions.

    Science.gov (United States)

    Zampieri, Fernando Godinho; Park, Marcelo; Azevedo, Luciano Cesar Pontes

    2013-05-01

    Colloids are frequently used for fluid expansion in the intensive care unit, although its use on several clinical scenarios remains unproven of any relevant clinical benefit. The purpose of this article was to carry out a narrative review regarding the safety and efficacy of colloids in patients with sepsis and septic shock, with emphasis on the most commonly used colloids, albumin and starches. Colloids are effective fluid expanders and are able to restore the hemodynamic profile with less total volume than crystalloids. These properties appear to be preserved even in patients with sepsis with increased capillary permeability. However, some colloids are associated with renal impairment and coagulation abnormalities. Starch use was associated with increased mortality in two large clinical trials. Also, starches probably have significant renal adverse effects and may be related to more need for renal replacement therapy in severe sepsis. Albumin is the only colloid that has been shown safe in patients with sepsis and that may be associated with improved outcomes on specific subpopulations. No trial so far found any robust clinical end point favoring colloid use in patients with sepsis. Because there is no proven benefit of the use of most colloids in patients with sepsis, its use should not be encouraged outside clinical trials. Albumin is the only colloid solution that has proven to be safe, and its use may be considered on hypoalbuminemic patients with sepsis. Nevertheless, there are no robust data to recommend routine albumin administration in sepsis. Starch use should be avoided in patients with sepsis because of the recent findings of a multicenter randomized study until further evidence is available.

  17. Implications of the new sepsis definition on research and practice.

    Science.gov (United States)

    Peach, Brian C

    2017-04-01

    The Society of Critical-Care Medicine and the European Society of Intensive Care Medicine recently announced a marked change in the sepsis definition. A task force of 19 sepsis clinicians and researchers made the change based on advances in the pathobiological understanding of the septic process. The task force determined that there were numerous justifications for a revision of the sepsis definition, which are outlined in this article. The systemic inflammatory response criteria have been replaced by the Sequential Organ Failure Assessment (SOFA) score in the newly operationalized definition (Singer et al., 2016). In addition to the definition change, the task force recommended using the new quick SOFA (qSOFA) score in non-ICU settings, as a risk stratification tool to identify patients who may be septic or be at risk of developing sepsis. The change in definition will likely have a negative impact on sepsis research in the short-term as hospitals adjust their coding for the new definition, but may result in less misclassification bias and improved research data in the long-term. While the intent of the SCCM/ESICM task force was to better define sepsis for coding and epidemiological research purposes, there is the potential for improved patient outcomes if clinicians are better able to differentiate between sepsis and inflammatory events. The qSOFA tool may also aid clinicians in recognizing sepsis in a quicker manner, leading to more timely treatment, and potentially better outcomes. While the new operationalized Sepsis-3 definition appears on the surface to be an improvement over the previous iterations, it remains to be seen if research data will be more robust using the new criteria. There is the potential for better patient outcomes if clinicians are better able to differentiate sepsis from inflammatory events with the new definition, and if sepsis cases are recognized sooner with qSOFA. Future research on the impact of this definition change on research and

  18. Pantoea dispersa: an unusual cause of neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Veerendra Mehar

    Full Text Available Neonatal septicemia is the most important cause of neonatal mortality. A wide variety of bacteria both aerobic and anaerobic can cause neonatal sepsis. Genus Pantoea is a member of Enterobacteriaceae family that inhabits plants, soil and water and rarely causes human infections, however, Pantoea dispersa has not been reported as a causative organism for neonatal sepsis. We hereby report two neonates with early onset sepsis caused by Pantoea dispersa. Early detection and appropriate antibiotic therapy can improve overall outcome of this rare infection in neonates.

  19. Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

    DEFF Research Database (Denmark)

    Kofoed, Kristian

    2008-01-01

    of sepsis is of great importance for choice of treatment, level of monitoring and prognosis. In this biomarkers could be a significant aid, and thus the search for and application of "new" sepsis biomarkers is of great importance. The thesis reviews the definitions and the epidemiology, and gives...... an overview of the immunology of sepsis with emphasis on the suggested roles of the soluble fractions of triggering receptor expressed on myeloide cells-1 (sTREM-1), urokinase-type plasminogen activator receptor (suPAR), and the cytokine macrophage migration inhibitory factor (MIF). The Luminex technology...

  20. A Study of Incidenceof Post-oparative Sepsis In Iran

    Directory of Open Access Journals (Sweden)

    H. Hashemian

    1966-01-01

    Full Text Available A survey was .carried out to determine the incidence of sepsis after surgical operation. A total of 133 cases were studied. 33 percent of elean wounds w~reqffected by some. post operative sepsis and yielded pathogenic bacteria on culture. Staphylococcus aureus was the most common pathogen but pseudomonas and E. coli were also common. Cultures were taken from the staff, the environment and objects and an attempt was made to show the significance of each in connection with hospital cross infection. Finally certain recommendations were made in the hope that the observance of these specific rules would significantly lower the rate of sepsis at the particular hospital concerned

  1. Systematic review of use of β-blockers in sepsis

    Directory of Open Access Journals (Sweden)

    Cyril Jacob Chacko

    2015-01-01

    Conclusion: There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

  2. 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.

  3. Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

    Science.gov (United States)

    Hamed, Sonja; Behnes, Michael; Pauly, Dominic; Lepiorz, Dominic; Barre, Max; Becher, Tobias; Lang, Siegfried; Akin, Ibrahim; Borggrefe, Martin; Bertsch, Thomas; Hoffmann, Ursula

    2017-08-09

    Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. NCT01535534 . Registered 14.02.2012.

  4. Totem and taboo: fluids in sepsis.

    Science.gov (United States)

    Hilton, Andrew K; Bellomo, Rinaldo

    2011-01-01

    The need for early, rapid, and substantial fluid resuscitation in septic patients has long been an article of faith in the intensive care community, a tribal totem that is taboo to question. The results of a recent multicenter trial in septic children in Africa, published in The New England Journal of Medicine, powerfully challenge the fluid paradigm. The salient aspects of the trial need to be understood and reflected upon. In this commentary, we discuss the background to and findings of the trial and explain why they will likely trigger a re-evaluation of our thinking about fluids in sepsis, a re-evaluation that is already happening in the treatment of acute respiratory distress syndrome and acute kidney injury and in postoperative care.

  5. An Immunological Perspective on Neonatal Sepsis

    Science.gov (United States)

    Kan, Bernard; Razzaghian, Hamid; Lavoie, Pascal M.

    2016-01-01

    Despite concerted international efforts, mortality from neonatal infections remains unacceptably high in some areas of the world, particularly for premature infants. Recent developments in flow cytometry and next-generation sequencing technologies have led to major discoveries over the past few years, providing a more integrated understanding of the developing human immune system in the context of its microbial environment. We review these recent findings, focusing on how in human newborns incomplete maturation of the immune system before a full term of gestation impacts on their vulnerability to infection. We also discuss some of the clinical implications of this research in guiding the design of more-accurate age-adapted diagnostic and preventive strategies for neonatal sepsis. PMID:26993220

  6. Sepse: atualidades e perspectivas Sepsis: an update

    Directory of Open Access Journals (Sweden)

    Rodrigo Siqueira-Batista

    2011-06-01

    Full Text Available O objetivo do presente artigo é oferecer uma atualização dos principais aspectos da sepse, complicação infecciosa extremamente importante do ponto de vista da clínica e da saúde pública. Algumas hipóteses têm sido propostas para explicar sua gênese, as quais encerram aspectos referentes a interação microrganismo/sistema imune inato, a inflamação/mediação imunológica e o sistema de coagulação. As manifestações clínicas são variadas e dependem do local primário da infecção. A identificação precoce dos sinais e sintomas é de crucial importância para a instituição de medidas terapêuticas que se baseiam, fundamentalmente, em reposição volêmica, antibioticoterapia, emprego de costicosteróides, tratamento anticoagulante, medidas de manutenção da viabilidade biológica e suporte nutricional.This paper aims to provide an update on the main aspects of sepsis, a very relevant health care issue. A number of hypotheses have been proposed to explain its origin, involving interactions between microorganisms and the innate immune system, inflammation/immune mediation and the coagulation system. The clinical features of sepsis are variable and depend on the primary site of infection. The identification of early signs and symptoms is crucial for starting therapeutic measures fundamentally based on volume resuscitation, antibiotic therapy, use of steroids, anticoagulant therapy, biologic viability maintenance interventions and nutritional support.

  7. In-111 WBC imaging in musculoskeletal sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, L.; Ouzounian, T.J.; Webber, M.M.; Amstutz, H.C.

    1984-01-01

    This study evaluated the accuracy and utility of the In-111 labeled WBC imaging in a series of patients who were suspected of having musculoskeletal sepsis. The labeling of the WBCs was patterned after a method previously described, in which the WBCs are labeled with In-111 oxine in plasma. The WBCs from 100 ml of blood are separated and incubated with In-111 oxine complex, and then 500 ..mu..Ci. of the labeled cells were reinjected into the patient. Images of the areas in question were obtained at 24 hrs. In some instances, 48 hour images were also obtained. Images were interpreted using consistent criteria. Forty imaging procedures were done on 39 patients. These included 39 total joint protheses, and 17 other images to evaluate possible osteomyelitis, septic arthritis or deep abscesses. Of these studies, 15 were positive, and 42 negative. The findings were then correlated with operative culture and pathology in 21, aspiration cultures and gram stains in 14, and with clinical findings in the remaining 21. This correlation showed 41 true negatives, 12 true positives, 1 false negative, and 2 false positives. The sensitivity was 92.9% and the specificity was 95.2%l. The false negative occurred in a patient on chronic suppressive antibiotic therapy for an infected total hip replacement. The false positive images occurred in a patient with active rheumatoid arthritis and in a patient imaged one month post operative placement of the prosthesis. These images were very useful in several septic patients who had many possible sites of infection. The authors conclude that In-III imaging is an accurate and useful non-invasive method of evaluating musculoskeletal sepsis.

  8. An A2A adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models

    Directory of Open Access Journals (Sweden)

    Linden Joel

    2008-10-01

    Full Text Available Abstract Background The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A2A adenosine receptor (AR agonist treated and untreated animals during experimental sepsis. Methods Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus or lipopolysaccharide (LPS. Mice inoculated with live bacteria were treated with an A2A AR agonist (ATL313 or phosphate buffered saline (PBS, with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days. Results There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013 or S. aureus (60% vs. 20%, p = 0.02 when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005. The serum concentrations of TNF-α, MIP-1α, MCP-1, IFN-γ, and IL-17 were decreased by ATL313 after LPS injection (p p p Conclusion Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.

  9. Arginine and Citrulline and the Immune Response in Sepsis

    Directory of Open Access Journals (Sweden)

    Karolina A.P. Wijnands

    2015-02-01

    Full Text Available Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target.

  10. Development of a magnetic lab-on-a-chip for point-of-care sepsis diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Schotter, Joerg [Austrian Research Centers GmbH-ARC, Nano-System-Technologies, Donau-City-Strasse 1, Tech Gate Vienna 2. OG, 1220 Vienna (Austria)], E-mail: Joerg.Schotter@arcs.ac.at; Shoshi, Astrit; Brueckl, Hubert [Austrian Research Centers GmbH-ARC, Nano-System-Technologies, Donau-City-Strasse 1, Tech Gate Vienna 2. OG, 1220 Vienna (Austria)

    2009-05-15

    We present design criteria, operation principles and experimental examples of magnetic marker manipulation for our magnetic lab-on-a-chip prototype. It incorporates both magnetic sample preparation and detection by embedded GMR-type magnetoresistive sensors and is optimized for the automated point-of-care detection of four different sepsis-indicative cytokines directly from about 5 {mu}l of whole blood. The sample volume, magnetic particle size and cytokine concentration determine the microfluidic volume, sensor size and dimensioning of the magnetic gradient field generators. By optimizing these parameters to the specific diagnostic task, best performance is expected with respect to sensitivity, analysis time and reproducibility.

  11. Development of a magnetic lab-on-a-chip for point-of-care sepsis diagnosis

    Science.gov (United States)

    Schotter, Joerg; Shoshi, Astrit; Brueckl, Hubert

    2009-05-01

    We present design criteria, operation principles and experimental examples of magnetic marker manipulation for our magnetic lab-on-a-chip prototype. It incorporates both magnetic sample preparation and detection by embedded GMR-type magnetoresistive sensors and is optimized for the automated point-of-care detection of four different sepsis-indicative cytokines directly from about 5 μl of whole blood. The sample volume, magnetic particle size and cytokine concentration determine the microfluidic volume, sensor size and dimensioning of the magnetic gradient field generators. By optimizing these parameters to the specific diagnostic task, best performance is expected with respect to sensitivity, analysis time and reproducibility.

  12. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis

    Directory of Open Access Journals (Sweden)

    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.

  13. Prevalence and factors associated with neonatal sepsis among ...

    African Journals Online (AJOL)

    Prevalence and factors associated with neonatal sepsis among neonates in Temeke and Mwananyamala Hospitals in Dar es Salaam, Tanzania. Asia Jabiri, Herman L. Wella, Avelina Semiono, Adellah Saria, Joyce Protas ...

  14. 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.

  15. Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

    DEFF Research Database (Denmark)

    Kofoed, Kristian

    2008-01-01

    of sepsis is of great importance for choice of treatment, level of monitoring and prognosis. In this biomarkers could be a significant aid, and thus the search for and application of "new" sepsis biomarkers is of great importance. The thesis reviews the definitions and the epidemiology, and gives...... an overview of the immunology of sepsis with emphasis on the suggested roles of the soluble fractions of triggering receptor expressed on myeloide cells-1 (sTREM-1), urokinase-type plasminogen activator receptor (suPAR), and the cytokine macrophage migration inhibitory factor (MIF). The Luminex technology...... is described, it is explained how a multiplex assay is developed and validated, and based on our experience and on the literature the advantages and shortcomings of the method are discussed. In the last part the results of the two clinical studies on 161 patients suspected of sepsis are put into the context...

  16. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    OBJECTIVE: To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis. DESIGN: A prospective study of mortality in patients with sepsis whose serum levels of sL-selectin were measured on admission to an intensive care unit (ICU) and 4 days later. Follow-up data......, and 3 and 12 months after admission. Serum sL-selectin levels were significantly lower in the patients than in the controls. Sepsis nonsurvivors had significantly lower levels than survivors. Efficiency analysis and receiver operation characteristics showed that the ideal cutoff point for s......L-selectin as a test for sepsis survival was 470 ng/ml. The accumulated mortality in patients with subnormal sL-selectin levels on admission was significantly increased. No correlation was found between clinical or paraclinical markers, including SAPS II and sL-selectin, and no relationship to the microbial diagnosis...

  17. Picroside II protects against sepsis via suppressing inflammation in mice

    Science.gov (United States)

    Huang, Ying; Zhou, Miao; Li, Chengbao; Chen, Yuanli; Fang, Wei; Xu, Guo; Shi, Xueyin

    2016-01-01

    Picroside II, an iridoid compound extracted from Picrorhiza, exhibits anti-inflammatory and anti-apoptotic activities. We explored the protective effects and mechanisms of picroside II in a mouse model of sepsis induced by cecal ligation and puncture (CLP), using three groups of mice: Group A (sham), Group B (CLP+NS) and Group C (CLP+20 mg/kg picroside II). The mortality in mice with sepsis was decreased by the administration of picroside II, and lung injury was alleviated simultaneously. Picroside II treatment enhanced bacterial clearance in septic mice. Further, picroside II treatment alleviated the inflammatory response in sepsis and enhanced immune function by inhibiting the activation of NLRP3 inflammasome and NF-κB pathways. Picroside II may represent an anti-inflammatory drug candidate, providing novel insight into the treatment of sepsis. PMID:28078023

  18. Impact of CT in patients with sepsis of unknown origin

    Energy Technology Data Exchange (ETDEWEB)

    Barkhausen, J.; Stoeblen, F.; Mueller, R.D. [University Hospital Essen (Germany). Dept. of Radiology; Dominguez-Fernandez, E. [University Hospital Essen (Germany). Dept. of General Surgery; Henseke, P. [Nycomed-Amersham Arzneimittel GmbH, Muenchen (Germany)

    1999-09-01

    Purpose: To evaluate the diagnostic relevance of CT in patients with sepsis of unknown origin. Material and Methods: Sixty-three consecutive intensive care patients with suspicion of an abscess and negative or inconclusive previous radiological examinations were included. CT was performed using the helical technique. A total of 45 abdominal and 38 chest examinations were evaluated. Results: 5/38 examinations of the chest revealed the source of sepsis (pleural empyema 2, lung abscess 1, mediastinitis 1, retrosternal abscess 1). 7/45 abdominal CT examinations showed the source of sepsis (intraabdominal abscess 2, hepatic abscess 3, intestinal perforation 1, gangrenous colitis 1). Conclusion: CT is useful for the evaluation of patients with fever or sepsis without a known source. Due to the detection of a spetic focus by CT, 19% of the patients in our study could be immediately referred to causal therapy as percutaneous drainage or surgery. (orig.)

  19. Government introduces action plan to reduce deaths from sepsis.

    Science.gov (United States)

    Kleebauer, Alistair

    2015-01-20

    Tackling sepsis - the potentially fatal over-reaction of the immune system to infection - must be given the same priority as reducing Clostridium difficile and MRSA infections, the government has said.

  20. Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis

    Directory of Open Access Journals (Sweden)

    Takayuki Okamoto

    2012-01-01

    Full Text Available Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the endothelial microenvironment in an anti-inflammatory and anticoagulant state. A recombinant soluble form of thrombomodulin has been approved to treat patients suffering from disseminated intravascular coagulation (DIC and has thus far shown greater therapeutic potential than heparin. A phase II clinical trial is currently underway in the USA to study the efficacy of thrombomodulin for the treatment of sepsis with DIC complications. This paper focuses on the critical roles that thrombomodulin plays at the intersection of inflammation and coagulation and proposes the possible existence of interactions with integrins via protein C. Finally, we provide a rationale for the clinical application of thrombomodulin for alleviating sepsis.

  1. Opening the microcirculation: can vasodilators be useful in sepsis?

    NARCIS (Netherlands)

    Buwalda, Mattijn; Ince, Can

    2002-01-01

    Objective: A prominent feature of sepsis is dysfunction of the microcirculation, with impaired perfusion and regional tissue oxygenation causing a deficit in oxygen extraction. If shunting of oxygen transport past closed hypoxic microcirculatory beds is responsible for this, vasodilator therapy,

  2. Development of an e-learning package for sepsis care.

    Science.gov (United States)

    Davis, Anna; Henderson, James; Langmack, Gill

    Severe sepsis is a major cause of morbidity and mortality in the UK. This article describes the collaborative development and implementation of an interactive online learning package to understand the key role nurses have in recognising and then starting to apply the Sepsis Six care bundle in clinical practice. The e-learning package, developed in a UK teaching hospital, uses a case study approach to address the knowledge that is required to be able to recognise sepsis, to understand the processes that occur and the ongoing care and treatment required. The package is relevant to final-year student nurses, newly registered nurses in preceptorship and other health professionals involved in assessing and treating patients who may be developing sepsis.

  3. Procalcitonina como marcador de sepsis en niños

    National Research Council Canada - National Science Library

    Diana González Rangel; Germán Camacho Moreno; Omar Quintero Guevara

    2016-01-01

      Background. Procalcitonin is a biomarker of severe bacterial infection and sepsis, with diagnostic, monitoring, severity and prognosis applications, that shows values of sensitivity, specicity and variable cutoff in children...

  4. Lymphocyte integrin expression differences between SIRS and sepsis patients.

    Science.gov (United States)

    Heffernan, D S; Monaghan, S F; Ayala, Alfred

    2017-11-01

    Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3+ T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3+ T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3+ T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3+CD29+ T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

  5. Hospital-related cost of sepsis: A systematic review.

    Science.gov (United States)

    Arefian, Habibollah; Heublein, Steffen; Scherag, André; Brunkhorst, Frank Martin; Younis, Mustafa Z; Moerer, Onnen; Fischer, Dagmar; Hartmann, Michael

    2017-02-01

    This article systematically reviews research on the costs of sepsis and, as a secondary aim, evaluates the quality of economic evaluations reported in peer-reviewed journals. We systematically searched the MEDLINE, National Health Service (Abstracts of Reviews of Effects, Economic Evaluation and Health Technology Assessment), Cost-effectiveness Analysis Registry and Web of Knowledge databases for studies published between January 2005 and June 2015. We selected original articles that provided cost and cost-effectiveness analyses, defined sepsis and described their cost calculation method. Only studies that considered index admissions and re-admissions in the first 30 days were published in peer-reviewed journals and used standard treatments were considered. All costs were adjusted to 2014 US dollars. Medians and interquartile ranges (IQRs) for various costs of sepsis were calculated. The quality of economic studies was assessed using the Drummond 10-item checklist. Overall, 37 studies met our eligibility criteria. The median of the mean hospital-wide cost of sepsis per patient was $32,421 (IQR $20,745-$40,835), and the median of the mean ICU cost of sepsis per patient was $27,461 (IQR $16,007-$31,251). Overall, the quality of economic studies was low. Estimates of the hospital-related costs of sepsis varied considerably across the included studies depending on the method used for cost calculation, the type of sepsis and the population that was examined. A standard model for conducting cost improve the quality of studies on the costs of sepsis. Copyright © 2016 The British Infection Association. All rights reserved.

  6. 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....

  7. Spontaneous blood pressure oscillations in mechanically ventilated patients with sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Plovsing, Ronni R; Greve, Anders M

    2016-01-01

    OBJECTIVE: In the present hypothesis-generating study, we investigated whether spontaneous blood pressure oscillations are suppressed to lower frequencies, and whether abolished oscillations are associated with an adverse outcome in mechanically ventilated patients with sepsis. METHODS: We...... retrospectively subjected invasive steady-state blood pressure recordings from 65 mechanically ventilated patients with sepsis to spectral analysis. Modified spectral bands were visually identified by plotting spectral power against frequency. RESULTS: Modified middle-frequency and low-frequency (MF' and LF...

  8. Development and Validation of an Automated Sepsis Risk Assessment System.

    Science.gov (United States)

    Back, Ji-Sun; Jin, Yinji; Jin, Taixian; Lee, Sun-Mi

    2016-10-01

    Aggressive resuscitation can decrease sepsis mortality, but its success depends on early detection of sepsis. The purpose of this study was to develop and verify an Automated Sepsis Risk Assessment System (Auto-SepRAS), which would automatically assess the sepsis risk of inpatients by applying data mining techniques to electronic health records (EHR) data and provide daily updates. The seven predictors included in the Auto-SepRAS after initial analysis were admission via the emergency department, which had the highest odds ratio; diastolic blood pressure; length of stay; respiratory rate; heart rate; and age. Auto-SepRAS classifies inpatients into three risk levels (high, moderate, and low) based on the predictive values from the sepsis risk-scoring algorithm. The sepsis risk for each patient is presented on the nursing screen of the EHR. The AutoSepRAS was implemented retrospectively in several stages using EHR data and its cut-off scores adjusted. Overall discrimination power was moderate (AUC>.80). The Auto-SepRAS should be verified or updated continuously or intermittently to maintain high predictive performance, but it does not require invasive tests or data input by nurses that would require additional time. Nurses are able to provide patients with nursing care appropriate to their risk levels by using the sepsis risk information provided by the Auto-SepRAS. In particular, with early detection of changes related to sepsis, nurses should be able to help in providing rapid initial resuscitation of high-risk patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Molecular diagnosis of sepsis: New aspects and recent developments

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    Lehman, L.; Hunfeld, K.-P.; Kost, G.

    2014-01-01

    By shortening the time to pathogen identification and allowing for detection of organisms missed by blood culture, new molecular methods may provide clinical benefits for the management of patients with sepsis. While a number of reviews on the diagnosis of sepsis have recently been published we here present up-to-date new developments including multiplex PCR, mass spectrometry and array techniques. We focus on those techniques that are commercially available and for which clinical studies have been performed and published. PMID:24678402

  10. New Translational Research Provides Insights into Liver Dysfunction in Sepsis

    OpenAIRE

    Peter Recknagel; Gonnert, Falk A.; Martin Westermann; Sandro Lambeck; Amelie Lupp; Alain Rudiger; Alex Dyson; Carré, Jane E.; Andreas Kortgen; Christoph Krafft; Jürgen Popp; Christoph Sponholz; Valentin Fuhrmann; Ingrid Hilger; Claus, Ralf A

    2012-01-01

    Editors' Summary Background Sepsis (blood poisoning)—a life-threatening condition caused by an inappropriate immune response to an infection—is a major global cause of death. Normally, when bacteria or other microbes enter the human body, the immune system efficiently destroys the invaders. In sepsis the immune system goes into overdrive, and the chemicals it releases into the blood to combat the infection trigger widespread inflammation (swelling). This leads to the formation of small blood ...

  11. Puerperal sepsis--still a major threat for parturient.

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    Shamshad; Shamsher, Saadia; Rauf, Bushara

    2010-01-01

    Puerperal sepsis is one of the leading causes of preventable maternal morbidity and mortality. It is still ranked as 3rd major cause of maternal deaths in our country. The objective of this study was to evaluate morbidity and mortality from puerperal sepsis and to identify its risk factors. This observational study was carried out in Ayub Teaching Hospital over a period of three years. All patients admitted with diagnosis of puerperal sepsis secondary to genital tract infection were evaluated with thorough details of history and examination to determine their demographic details, obstetrical profiles, presenting features, state of infectious morbidity, need for intervention and mortality related to puerperal sepsis. Puerperal sepsis was 1.7% of all obstetrical admissions and 34.4% of postnatal complications. It was seen common among young patients of 15-25 years age. 61 (66.3%), of lower parity, 58 (63.00%), low socioeconomic status, 60 (65.20%), uneducated patients, 72 (78.20%), home deliveries, 68 (73.90%), prolong labour, 54 (58.60), prolong rupture of membranes from 48-72 hours, 68 (73.8%) and deliveries conducted by untrained birth attendants, 57 (60.5%). Puerperal sepsis morbidity was mostly foul smelling discharge, 23 (25%), retained product of conception, 41 (44.5%), peritonitis, 8 (8.60%), septicaemia, 4 (4.3%), pelvic abscess, 10 (10.80%), endotoxic shock, 4 (4.30%), disseminated intravascular coagulation, 2 (2.1%). Sepsis related mortality was 6/42 (14.2%). Puerperal sepsis is an important public health problem contributing to maternal morbidity and mortality. Majority of predisposing factors are preventable. Optimal antiseptic measures and careful monitoring are needed throughout the process of labour.

  12. Gene Expression Profiles Differentiate Between Sterile SIRS and Early Sepsis

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    Johnson, Steven B.; Lissauer, Matthew; Bochicchio, Grant V.; Moore, Richard; Cross, Alan S.; Scalea, Thomas M.

    2007-01-01

    Introduction: The systemic inflammatory response syndrome (SIRS) occurs frequently in critically ill patients and presents similar clinical appearances despite diverse infectious and noninfectious etiologies. Despite similar phenotypic expression, these diverse SIRS etiologies may induce divergent genotypic expressions. We hypothesized that gene expression differences are present between sepsis and uninfected SIRS prior to the clinical appearance of sepsis. Methods: Critically ill uninfected SIRS patients were followed longitudinally for the development of sepsis. All patients had whole blood collected daily for gene expression analysis by Affymetrix Hg_U133 2.0 Plus microarrays. SIRS patients developing sepsis were compared with those remaining uninfected for differences in gene expression at study entry and daily for 3 days prior to conversion to sepsis. Acceptance criteria for differentially expressed genes required: >1.2 median fold change between groups and significance on univariate and multivariate analysis. Differentially expressed genes were annotated to pathways using DAVID 2.0/EASE analysis. Results: A total of 12,782 (23.4%) gene probes were differentially expressed on univariate analysis 0 to 48 hours before clinical sepsis. 626 (1.1%) probes met acceptance criteria, corresponding to 459 unique genes, 65 (14.2%) down and 395 (85.8%) up expressed. These genes annotated to 10 pathways that functionally categorized to 4 themes involving innate immunity, cytokine receptors, T cell differentiation, and protein synthesis regulation. Conclusions: Sepsis has a unique gene expression profile that is different from uninfected inflammation and becomes apparent prior to expression of the clinical sepsis phenotype. PMID:17414611

  13. A Review of GM-CSF Therapy in Sepsis

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    Mathias, Brittany; Szpila, Benjamin E.; Moore, Frederick A.; Efron, Philip A.; Moldawer, Lyle L.

    2015-01-01

    Abstract Determine what clinical role, if any, GM-CSF may have in the clinical treatment of sepsis in the adult patient. Advancements in the management of sepsis have led to significant decreases in early mortality; however, sepsis remains a significant source of long-term mortality and disability which places strain on healthcare resources with a substantial growing economic impact. Historically, early multiple organ failure (MOF) and death in patients with severe sepsis was thought to result from an exaggerated proinflammatory response called the systemic inflammatory response syndrome (SIRS). Numerous prospective randomized controlled trials (PRCTs) tested therapies aimed at decreasing the organ injury associated with an exaggerated inflammatory response. With few exceptions, the results from these PRCTs have been disappointing, and currently no specific therapeutic agent is approved to counteract the early SIRS response in patients with severe sepsis. It has long been recognized that there is a delayed immunosuppressive state that contributes to long-term morbidity. However, recent findings now support a concurrent proinflammatory and anti-inflammatory response present throughout sepsis. Multiple immunomodulating agents have been studied to combat the immunosuppressive phase of sepsis with the goal of decreasing secondary infection, reducing organ dysfunction, decreasing ICU stays, and improving survival. Granulocyte-macrophage colony stimulating factor (GM-CSF), a myelopoietic growth factor currently used in patients with neutropenia secondary to chemotherapy-induced myelosuppression, has been studied as a potential immune-activating agent. The applicability of GM-CSF as a standard therapy for generalized sepsis is still largely understudied; however, small-scale studies available have demonstrated some improved recovery from infection, decreased hospital length of stay, decreased days requiring mechanical ventilation, and decreased medical costs. PMID

  14. 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

  15. Immunosuppression after sepsis: systemic inflammation and sepsis induce a loss of naïve 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.

  16. Current trends in inflammatory and immunomodulatory mediators in sepsis

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    Aziz, Monowar; Jacob, Asha; Yang, Weng-Lang; Matsuda, Akihisa; Wang, Ping

    2013-01-01

    Sepsis refers to severe systemic inflammation in response to invading pathogens. An overwhelming immune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple organ damage, and even death. Cytokines, proteases, lipid mediators, gaseous substances, vasoactive peptides, and cell stress markers play key roles in sepsis pathophysiology. Various adhesion molecules and chemokines sequester and activate neutrophils into the target organs, further augmenting inflammation and tissue damage. Although the anti-inflammatory substances counterbalance proinflammatory mediators, prolonged immune modulation may cause host susceptibility to concurrent infections, thus reflecting enormous challenge toward developing effective clinical therapy against sepsis. To understand the complex interplay between pro- and anti-inflammatory phenomenon in sepsis, there is still an unmet need to study newly characterized mediators. In addition, revealing the current trends of novel mediators will upgrade our understanding on their signal transduction, cross-talk, and synergistic and immunomodulating roles during sepsis. This review highlights the latest discoveries of the mediators in sepsis linking to innate and adaptive immune systems, which may lead to resolution of many unexplored queries. PMID:23136259

  17. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers

    Science.gov (United States)

    Bauer, Michael; Riedemann, Niels C.; Hartog, Christiane S.

    2012-01-01

    Summary: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

  18. Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis

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    Sang Hoon Lee

    2015-01-01

    Full Text Available Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n=19] and septic shock [n=98] who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG, high-density lipoprotein (HDL, low-density lipoprotein (LDL, free fatty acid (FFA, and apolipoprotein (Apo A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p=0.043, p=0.020, p=0.005, and p=0.015, resp.. According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p=0.018 and p=0.008, resp.. Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.

  19. Interleukin-6: A Sensitive Parameter for the Early Detection of Neonatal Sepsis

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    M Khaled Noor

    2009-11-01

    Full Text Available Background: Neonatal sepsis is a major cause of neonatal mortality and morbidity throughout the world. Though blood culture is the gold standard and has higher sensitivity and specificity over the hematological value and cytokine, it is not available in our community health situation and also in most of health care facilities. It is also time consuming. Therefore hematological value and interleukin-6 can be evaluated for the early diagnosis of neonatal bacterial infection. Objective: This study was conducted to see the usefulness of IL-6 as an early marker of neonatal sepsis and also to compare the sensitivity in comparison with CRP, hematological value and blood culture. Study Design: It was a quasy experimental study. Setting: This study was carried out in the neonatal unit of pediatric department, BSMMU during the period of September, 2005 to February, 2006. Method: Forty five suspected septic cases were enrolled in the study and thirty healthy newborn were taken for comparison. Venous blood sample from peripheral vein was collected on the 1st day of symptoms and/or 1st day of admission and was sent for IL-6 estimation within half an hour and estimation of IL-6 was done by using immunolyte DPC USA which employed automated chemiluminescent immunoassays. Results: Out of forty five cases of suspected-neonatal sepsis, IL-6 were positive in twenty five cases. In culture proven sepsis 100% cases had raised IL-6. In control group only five babies had raised IL-6. Three cases were culture positive, of which all were also positive for IL-6 (100%. Among the cases twenty six were CRP positive, of which twenty were also positive for IL-6 (76.92%. Conclusion: In the present study IL-6 was found to be an early marker of neonatal infection. Sensitivity was more than CRP and other hematological parameter in the first twenty four hours. Key words: Interleukin-6, Neonatal Sepsis.DOI: 10.3329/bsmmuj.v1i1.3687 BSMMU J 2008; 1(1: 1-5

  20. Decreased Tissue COX5B Expression and Mitochondrial Dysfunction during Sepsis-Induced Kidney Injury in Rats

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    Jochen Hinkelbein

    2017-01-01

    Full Text Available 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<0.01 were used for analysis of significantly regulated protein spots. MALDI-TOF in combination with peptide mass fingerprinting (PMF as well as Western Blot analysis was used for protein identification. Bioinformatic network analyses (STRING, GeneMania, and PCViz were used to describe protein-protein interactions. Results. 12 spots were identified with significantly altered proteins (P<0.01 in the three analyzed groups. Two spots could not be identified. Four different proteins were found significantly changed among the groups: major urinary protein (MUP5, 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.

  1. Morbilidad y mortalidad por sepsis neonatal precoz Morbidity and mortality from early neonatal sepsis

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    Nayvi Fernández Díaz

    2010-06-01

    Full Text Available INTRODUCCIÓN. Se realizó un estudio retrospectivo, transversal y descriptivo durante el quinquenio comprendido entre enero de 2003 y diciembre de 2007. El objetivo de la investigación fue caracterizar el comportamiento de los recién nacidos (RN con diagnóstico de infección neonatal de aparición precoz, atendidos en la Unidad de Cuidados Intensivos Neonatales del Hospital Provincial Docente Ginecoobstétrico de Matanzas. MÉTODOS. El universo de estudio estuvo constituido por los 13 362 recién nacidos vivos documentados durante los años 2003 al 2007. La muestra quedó conformada por los RN que ingresaron en la unidad de cuidados intensivos neonatales. RESULTADOS. Las tasas de incidencia y mortalidad por esta causa experimentaron un aumento en el quinquenio. Los pacientes diagnosticados fueron principalmente del sexo masculino, raza blanca y pretérminos de bajo peso. En más de la mitad de los casos se registraron factores perinatales de riesgo. La forma de presentación más frecuente fue la sepsis generalizada. Los complementarios resultaron positivos en las ¾ partes de los pacientes. El uso de dobutamina está por debajo de lo que indican las recomendaciones para el tratamiento de la sepsis neonatal y la ventilación mecánica comúnmente es complicada. CONCLUSIONES. Existen fuertes fundamentos teóricos que sustentan la necesidad del desarrollo de un protocolo de acción, para contribuir a la disminución de la tasa de morbilidad y mortalidad por sepsis neonatal precoz.INTRODUCTION. A retrospective, cross-sectional and descriptive study was conducted during the five-year period between January, 2003 and December, 2007. The aim of present paper was to characterize the behavior of the newborn (NB diagnosed with early neonatal infection seen in the Neonatal Intensive Care of Gynecology and Obstetrics Teaching Provincial Hospital, Matanzas province. METHODS. Study group included 13 362 live birth newborn documented from 2003 to 2007

  2. Circulating MicroRNA-223 Serum Levels Do Not Predict Sepsis or Survival in Patients with Critical Illness

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    Fabian Benz

    2015-01-01

    Full Text Available Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. Methods. We used i.v. injection of lipopolysaccharide (LPS as well as cecal pole ligation and puncture (CLP for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU. Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum

  3. Carbon Monoxide Improves Efficacy of Mesenchymal Stromal Cells During Sepsis by Production of Specialized Proresolving Lipid Mediators.

    Science.gov (United States)

    Tsoyi, Konstantin; Hall, Sean R R; Dalli, Jesmond; Colas, Romain A; Ghanta, Sailaja; Ith, Bonna; Coronata, Anna; Fredenburgh, Laura E; Baron, Rebecca M; Choi, Augustine M K; Serhan, Charles N; Liu, Xiaoli; Perrella, Mark A

    2016-12-01

    Mesenchymal stromal cells are being investigated as a cell-based therapy for a number of disease processes, with promising results in animal models of systemic inflammation and sepsis. Studies are ongoing to determine ways to further improve the therapeutic potential of mesenchymal stromal cells. A gas molecule that improves outcome in experimental sepsis is carbon monoxide. We hypothesized that preconditioning of mesenchymal stromal cells with carbon monoxide ex vivo would promote further therapeutic benefit when cells are administered in vivo after the onset of polymicrobial sepsis in mice. Animal study and primary cell culture. Laboratory investigation. BALB/c mice. Polymicrobial sepsis was induced by cecal ligation and puncture. Mesenchymal stromal cells, mesenchymal stromal cells-conditioned with carbon monoxide, fibroblasts, or fibroblasts-conditioned with carbon monoxide were delivered by tail vein injections to septic mice. The mice were assessed for survival, bacterial clearance, and the inflammatory response during sepsis in each of the groups. Mesenchymal stromal cells were also assessed for their ability to promote bacterial phagocytosis by neutrophils, the production of specialized proresolving lipid mediators, and their importance for mesenchymal stromal cells function using gene silencing. Ex vivo preconditioning with carbon monoxide allowed mesenchymal stromal cells to be administered later after the onset of sepsis (6 hr), and yet maintain their therapeutic effect with increased survival. Carbon monoxide preconditioned mesenchymal stromal cells were also able to alleviate organ injury, improve bacterial clearance, and promote the resolution of inflammation. Mesenchymal stromal cells exposed to carbon monoxide, with docosahexaenoic acid substrate, produced specialized proresolving lipid mediators, particularly D-series resolvins, which promoted survival. Silencing of lipoxygenase pathways (5-lipoxygenase and 12/15-lipoxygenase), which are

  4. Circulating microRNA-223 serum levels do not predict sepsis or survival in patients with critical illness.

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    Benz, Fabian; Tacke, Frank; Luedde, Mark; Trautwein, Christian; Luedde, Tom; Koch, Alexander; Roderburg, Christoph

    2015-01-01

    Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis. We used i.v. injection of lipopolysaccharide (LPS) as well as cecal pole ligation and puncture (CLP) for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU). Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score) showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum levels do not reflect the presence of sepsis neither in mouse

  5. Microbiological procedures in the diagnostics of sepsis

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    Manica Müller Premru

    2013-07-01

    Full Text Available Background:Sepsis is one of the most serious bacterial infections. The diagnosis of sepsis is clinical. Microbiologists can detect bacteremia, which however is not present in all septic patients, by the procedure called blood culture.Methods:Blood culture is a semi-automated procedure of culturing blood in liquid media to detect and identify the causative agents. It is important to take 2 to 3 blood cultures with adequate volume of blood. The new, faster methods for bacterial identification from positive blood cultures and molecular methods for the detection of bacterial DNA directly from a blood sample are also becoming available.Results:In the years 2006 to 2011, the number of blood cultures obtained from patients in the University Medical Centre in Ljubljana, Institute of Oncology and the General hospital of Trbovlje (from 2007 was constantly increasing, from 18,404 in 2006 to 25,214 in 2011. The number of patients with positive blood culture/s increased from 1,033 in 2006 to 1,396 in 2011. The rate of blood culture positivity ranged from 10.9 % to 12.3 %. The ratio between gram-positive and gram-negative bacteria was approximately 50:50 %. In all the years under study, Escherichia coliwas the most frequent pathogenic isolate (19.2 % to 22.9 %, followed by Staphylococcus aureus(15.3 % to 17.4 %. Klebsiellaspp. represented 5.3 % to 8.3 % of isolates, Pseudomonas aeruginosa1.8 % to 3.4 %, Streptococcus pneumoniae2.9 % to 4.7 %, Enterococcusspp. 5.4 % to 8.1 %, anaerobes 2.1 % to 3.2 %. Coagulase-negative staphylococci decreased from 23.3 % to 16.9 %. Today, bacteria are identified by the fast and accurate method of mass spectrometry. Bacteria can alternativelly be detected directly from blood by the molecular tests.Conclusions:Blood culture is a very common procedure, its rate of positivity is stable. Among bacteria, the number and the proportion of pathogenic bacteria such as E. coli, S. aureusand S. pneumoniaeis increasing and the proportion

  6. Reconsidering lactate as a sepsis risk biomarker.

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    John L Moran

    Full Text Available There has been renewed interest in lactate as a risk biomarker in sepsis and septic shock. However, the ability of the odds ratio (OR and change in the area under the receiver operator characteristic curve (AUC-ROC to assess biomarker added-value has been questioned.A sepsis cohort was identified from the ICU database of an Australian tertiary referral hospital using APACHE III diagnostic codes. Demographic information, APACHE III scores, 24-hour post-admission patient lactate levels, and hospital mortality were accessed.Hospital mortality was modelled using a base predictive logistic regression model and sequential addition of admission lactate, lactate clearance ([lactateadmission-lactatefinal]/lactateadmission, and area under the lactate-time curve (LTC. Added-value was assessed using lactate index OR; AUC-ROC difference (base-model versus lactate index addition; net (mortality reclassification index (NRI; range -2 to +2; and net benefit (NB, the number of true positives per patient adjusted for the number of false positives. The data set comprised 717 patients with mean(SD age and APACHE III score 61.1(16.5 years and 68.3(28.2 respectively; 59.2% were male. Admission lactate was 2.3(2.5 mmol/l; with lactate of ≥ 4 mmol/L (37% hospital mortality in 17% and patients with lactate < 4 mmol/L having 18% hospital mortality. The admission base-model had an AUC-ROC = 0.81 with admission lactate OR = 1.127 (95%CI: 1.038, 1.224, AUC-ROC difference of 0.0032 (-0.0037, 0.01615; P = 0.61, and NRI 0.240(0.030, 0.464. The over-time model had an AUC-ROC = 0.86 with (i clearance OR = 0.771, 95%CI: 0.578, 1.030; P = 0.08; AUC-ROC difference 0.001 (-0.003, 0.014; P = 0.78, and NRI 0.109(-0.193, 0.425 and (ii LTC OR = 0.997, 95%CI: 0.989, 1.005, P = 0.49; AUC-ROC difference 0.004 (-0.002, 0.004; P = 0.34, and NRI 0.111(-0.222, 0.403. NB was not incremented by any lactate index.Lactate added-value assessment is dependent upon the performance of the underlying

  7. Targeting sepsis as a performance improvement metric: role of the nurse.

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    Kleinpell, Ruth; Schorr, Christa A

    2014-01-01

    Sepsis is the body's systemic response to infection that can be complicated by acute organ dysfunction and is associated with high mortality rates and adverse outcomes for acute and critically ill patients. The 2012 Surviving Sepsis Campaign guidelines advocated for implementation of evidence-based practice care for sepsis, with a focus on quality improvement. Nurses are directly involved in identification and management of sepsis. Implementing performance improvement strategies aimed at early recognition and targeted treatment can further improve sepsis care and patient outcomes. This article presents an overview of the process of implementing performance improvement initiatives for sepsis care, highlighting the significant contribution of nursing care.

  8. Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study Absolute counts of peripheral blood leukocyte subpopulations in intraabdominal sepsis and pneumonia-derived sepsis: a pilot study

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    Grazyna Anna Hoser

    2012-10-01

    Full Text Available The leading pathophysiological changes during sepsis include systemic abnormalities in the immune
    response. Due to the general character of these disturbances, sepsis is usually studied as a homogenous clinical
    condition. We aimed to compare the immune response in intraabdominal sepsis (IAS and pneumonia-derived
    sepsis (PDS. The following cell populations were examined: white blood cell count (WBC, monocytes, lymphocytes:
    CD3+, CD4+ and CD8+ T cells, B cells, and NK cells. In both studied groups (i.e. IAS and PDS, the
    WBC was elevated. However, it was significantly higher in the IAS group than in the PDS group. The difference
    was due to a lower granulocyte count, as well as a lower monocyte count in PDS. We found no significant
    correlation between the total lymphocyte number and CD3+CD8+ T cells in either form of sepsis. Similarly, we
    observed no correlation between the total lymphocyte number and the NK cells subset in IAS. However, the
    numbers of CD3+CD8+ and NK cells correlated similarly in both types of sepsis. Both studied types of sepsis
    induced profound lymphocytopenia, with marked loss of CD8+ T cells and the NK cells. However, the similar
    relation between them, which was independent of the infection type, suggests that the NK and CD3+CD8+ cells
    have shared mechanisms of regulation. The primary site of infection has an impact on the global immune reaction.
    These alternations include especially myeloid cells: granulocytes and monocytes which disappear from peripheral
    blood during PDS, but increase in IAS.
    The leading pathophysiological changes during sepsis include systemic abnormalities in the immune
    response. Due to the general character of these disturbances, sepsis is usually studied as a homogenous clinical
    condition. We aimed to compare the immune response in intraabdominal sepsis (IAS and pneumonia-derived
    sepsis (PDS. The following cell

  9. Enhanced Glycolytic Metabolism Contributes to Cardiac Dysfunction in Polymicrobial Sepsis.

    Science.gov (United States)

    Zheng, Zhibo; Ma, He; Zhang, Xia; Tu, Fei; Wang, Xiaohui; Ha, Tuanzhu; Fan, Min; Liu, Li; Xu, Jingjing; Yu, Kaijiang; Wang, Ruitao; Kalbfleisch, John; Kao, Race; Williams, David; Li, Chuanfu

    2017-05-01

    Cardiac dysfunction is present in >40% of sepsis patients and is associated with mortality rates of up to 70%. Recent evidence suggests that glycolytic metabolism plays a critical role in host defense and inflammation. Activation of Toll-like receptors on immune cells can enhance glycolytic metabolism. This study investigated whether modulation of glycolysis by inhibition of hexokinase will be beneficial to septic cardiomyopathy. Male C57B6/J mice were treated with a hexokinase inhibitor (2-deoxy-d-glucose [2-DG], 0.25-2 g/kg, n = 6-8) before cecal ligation and puncture (CLP) induced sepsis. Untreated septic mice served as control. Sham surgically operated mice treated with or without the 2-DG inhibitor served as sham controls. Cardiac function was assessed 6 hours after CLP sepsis by echocardiography. Serum was harvested for measurement of inflammatory cytokines and lactate. Sepsis-induced cardiac dysfunction was significantly attenuated by administration of 2-DG. Ejection fraction and fractional shortening in 2-DG-treated septic mice were significantly (P sepsis-increased serum levels of tumor necrosis factor α and interleukin 1β as well as lactate, and enhanced the expression of Sirt1 and Sirt3 in the myocardium, which play an important role in mitochondrial function and metabolism. In addition, 2-DG administration suppresses sepsis-increased expression of apoptotic inducers Bak and Bax as well as JNK phosphorylation in the myocardium. Glycolytic metabolism plays an important role in mediating sepsis-induced septic cardiomyopathy. The mechanisms may involve regulation of inflammatory response and apoptotic signaling.

  10. DJ-1/PARK7 Impairs Bacterial Clearance in Sepsis.

    Science.gov (United States)

    Amatullah, Hajera; Shan, Yuexin; Beauchamp, Brittany L; Gali, Patricia L; Gupta, Sahil; Maron-Gutierrez, Tatiana; Speck, Edwin R; Fox-Robichaud, Alison E; Tsang, Jennifer L Y; Mei, Shirley H J; Mak, Tak W; Rocco, Patricia R M; Semple, John W; Zhang, Haibo; Hu, Pingzhao; Marshall, John C; Stewart, Duncan J; Harper, Mary-Ellen; Liaw, Patricia C; Liles, W Conrad; Dos Santos, Claudia C

    2017-04-01

    Effective and rapid bacterial clearance is a fundamental determinant of outcomes in sepsis. DJ-1 is a well-established reactive oxygen species (ROS) scavenger. Because cellular ROS status is pivotal to inflammation and bacterial killing, we determined the role of DJ-1 in bacterial sepsis. We used cell and murine models with gain- and loss-of-function experiments, plasma, and cells from patients with sepsis. Stimulation of bone marrow-derived macrophages (BMMs) with endotoxin resulted in increased DJ-1 mRNA and protein expression. Cellular and mitochondrial ROS was increased in DJ-1-deficient ( -/- ) BMMs compared with wild-type. In a clinically relevant model of polymicrobial sepsis (cecal ligation and puncture), DJ-1 -/- mice had improved survival and bacterial clearance. DJ-1 -/- macrophages exhibited enhanced phagocytosis and bactericidal activity in vitro, and adoptive transfer of DJ-1 -/- bone marrow-derived mononuclear cells rescued wild-type mice from cecal ligation and puncture-induced mortality. In stimulated BMMs, DJ-1 inhibited ROS production by binding to p47 phox , a critical component of the NADPH oxidase complex, disrupting the complex and facilitating Nox2 (gp91 phox ) ubiquitination and degradation. Knocking down DJ-1 (siRNA) in THP-1 (human monocytic cell line) and polymorphonuclear cells from patients with sepsis enhanced bacterial killing and respiratory burst. DJ-1 protein levels were elevated in plasma from patients with sepsis. Higher levels of circulating DJ-1 were associated with increased organ failure and death. These novel findings reveal DJ-1 impairs optimal ROS production for bacterial killing with important implications for host survival in sepsis.

  11. The Timing of Early Antibiotics and Hospital Mortality in Sepsis.

    Science.gov (United States)

    Liu, Vincent X; Fielding-Singh, Vikram; Greene, John D; Baker, Jennifer M; Iwashyna, Theodore J; Bhattacharya, Jay; Escobar, Gabriel J

    2017-10-01

    Prior sepsis studies evaluating antibiotic timing have shown mixed results. To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

  12. Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography.

    Science.gov (United States)

    Panigada, Mauro; Zacchetti, Lucia; L'Acqua, Camilla; Cressoni, Massimo; Anzoletti, Massimo Boscolo; Bader, Rossella; Protti, Alessandro; Consonni, Dario; D'Angelo, Armando; Gattinoni, Luciano

    2015-01-01

    Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality. This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge. UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6-13) vs 5 (4-7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93-0.98, p = 0.003). Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality.

  13. Angiopoietin-2 associations with the underlying infection and sepsis severity.

    Science.gov (United States)

    Lymperopoulou, Korina; Velissaris, Dimitrios; Kotsaki, Antigone; Antypa, Elli; Georgiadou, Sara; Tsaganos, Thomas; Koulenti, Despina; Paggalou, Evgenia; Damoraki, Georgia; Karagiannidis, Napoleon; Orfanos, Stylianos E

    2015-05-01

    Angiopoietin-2 (Ang-2) is an important mediator in sepsis. We have previously shown that endotoxemia levels are related to the underlying infection and affect septic patients' outcome. Based on this background we now investigated if circulating Ang-2 (cAng-2) and monocyte Ang-2 expression in septic patients are associated with the underlying infection and organ failure. We measured cAng-2 in 288 septic patients (121 with sepsis, 167 with severe sepsis/septic shock) at less than 24h post study inclusion (day 1) and on days 3 and 7. Peripheral blood mononuclear cells (PBMCs) were additionally isolated; Ang-2 gene expression was estimated by means of real-time PCR. Levels of cAng-2 were higher under severe sepsis and septic shock, as compared to uncomplicated sepsis; PBMC Ang-2 copies were higher in severe sepsis. On day 1, cAng-2 and Ang-2 gene copies were greater under severe sepsis/septic shock in sufferers from all types of infections with the exception of community-acquired pneumonia and ventilator-associated pneumonia. cAng-2 increased proportionally to the number of failing organs, and was higher under metabolic acidosis and acute coagulopathy as compared to no failing organ. On day 1, copies of Ang-2 were higher in survivors, whereas cAng-2 was higher in non-survivors. In a large cohort of septic patients, cAng-2 kinetics appears associated with the underlying infection and organ failure type. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Neopterin Serum sebagai Prediktor Dini Luaran Perburukan pada Sepsis Neonatorum

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    Ahmad Hafidz

    2017-12-01

    Neopterin was known as the biomarker for diagnosed early onset neonatal sepsis. Nowadays it has been proven for neopterin as predictors of poor outcome in early and late neonatal sepsis. The objective of this study was to determine serum levels of neopterin as predictors of poor outcome in early and late neonatal sepsis. The study held from May to July 2017 in Dr. Hasan Sadikin General Hospital Bandung. All subjects were neonatal sepsis with Tollner score ≥10 observed for serum levels of neopterin with ELISA method and then followed during hospitalization. The outcome defined as good and poor outcomes. The data were analyzed using receiver operating characteristic (ROC for getting area under curved, cut-off point and also sensitivity, specificity. Research subjects consisted of 42 neonates, the majority which experienced poor outcomes were male (10 subjects, early onset sepsis (11 subjects, section cesarean procedure (11 subjects and were born in a hospital (14 subjects. Serum neopterin levels findings significantly correlated with poor outcomes. Mean of poor outcomes in sepsis was 60.97 ng/mL with observed levels 40.63–92.04 ng/mL. Area under the ROC curve of neopterin were 0.981 (95% CI=0.882–1.000; p43.13 with sensitivity 94.1% and specificity 96.0%. In conclusion, cut off levels of neopterin >43.13 with sensitivity 94.1% and specificity 96.0%. Neopterin defined as a biomarker for the early predictor of poor outcome in early and late onset neonatal sepsis.

  15. Improving the care of sepsis: Between system redesign and professional responsibility: A roundtable discussion in the world sepsis day, September 25, 2013, Riyadh, Saudi Arabia

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    Yaseen Arabi

    2014-01-01

    Full Text Available This paper summarizes the roundtable discussion in September 25, 2013, Riyadh, Saudi Arabia as part of the World Sepsis Day held in King Abdulaziz Medical City, Riyadh. The objectives of the roundtable discussion were to (1 review the chasm between the current management of sepsis and best practice, (2 discuss system redesign and role of the microsystem in sepsis management, (3 emphasize the multidisciplinary nature of the care of sepsis and that improvement of the care of sepsis is the responsibility of all, (4 discuss the bundle concept in sepsis management, and (5 reflect on the individual responsibility of the health care team toward sepsis with a focus on accountability and the moral agent.

  16. Incidence of thrombocytopenia and changes in various platelet parameters, in blood culture positive neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Sartaj Bhat

    2015-07-01

    Full Text Available Abstract Objective: To assess the incidence of thrombocytopenia and changes in various platelet parameters, in culture positive neonatal sepsis. Methods: This was prospective study conducted over a period of one year from December 2009 to November 2010 in neonatal intensive care unit of DDUH Hospital, a tertiary care hospital in Delhi, North India. All babies who were admitted during this period were evaluated prospectively for evidence of sepsis. Results: sepsis was diagnosed in 560 neonates. Among 560 neonates, 80/560 (14.28% had Culture positive sepsis. Out of 80 blood culture positive neonates 73 were term neonates and 7 were near term. Gram positive sepsis occurred in 21/80 (26.25%, gram negative sepsis in 54/80 (67.5%, and fungal sepsis in 5/80 (6.25%. Incidence of thrombocytopenia in Gram negative sepsis was (35/54 64.81%, in gram positive sepsis (15/21 71.41% and in fungal sepsis was (3/5 60%. Mean platelet count at the onset of sepsis in all the patients was 123287.5±49428.68. The mean duration of thrombocytopenia in gram positive sepsis was 4.66 ±2.6 days, in gram negative sepsis 4.39 ± 2.22 days and in fungal sepsis 5.2±1.3 days. MPV at the time of onset of sepsis (MPV was high in gram positive sepsis than in gram negative sepsis (11.57±0.88 Vs 11.29 ± 0.76. The MPV of thrombocytopenic neonates was significantly higher than that of non-thrombocytopenic neonates (p < 0.01.

  17. The diaphragm is better protected from oxidative stress than hindlimb skeletal muscle during CLP-induced sepsis.

    Science.gov (United States)

    Talarmin, Hélène; Derbré, Frédéric; Lefeuvre-Orfila, Luz; Léon, Karelle; Droguet, Mickaël; Pennec, Jean-Pierre; Giroux-Metgès, Marie-Agnès

    2017-09-01

    The aim of this study was to determine whether non-lethal sepsis induced by cecal ligation and puncture (CLP) modulates oxidative damage and enzymatic antioxidant defenses in diaphragm and hindlimb skeletal muscles (soleus and Extensor Digitorus Longus (EDL)). Female Wistar rats were divided into four experimental groups: (1) control animals, (2) animals sacrificed 2 hours or (3) 7 days after CLP, and (4) sham-operated animals. At the end of the experimental procedure, EDL, soleus, and diaphragm muscles were harvested and 4-hydroxynonenal (HNE)-protein adducts and protein carbonyl contents were examined in relation to superoxide dismutase and catalase expression and activities. We observed that both non-respiratory oxidative (i.e. soleus) and glycolytic skeletal muscles (i.e. EDL) are more susceptible to sepsis-induced oxidative stress than diaphragm, as attested by an increase in 4-HNE protein adducts and carbonylated proteins after 2 hours of CLP only in soleus and EDL. These differences could be explained by higher basal enzymatic antioxidant activities in diaphragm compared to hindlimb skeletal muscles. Together, these results demonstrate that diaphragm is better protected from oxidative stress than hindlimb skeletal muscles during CLP-induced sepsis.

  18. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey.

    Science.gov (United States)

    Iba, Toshiaki; Nisio, Marcello Di; Levy, Jerrold H; Kitamura, Naoya; Thachil, Jecko

    2017-09-27

    Recent clinical studies have shown that anticoagulant therapy might be effective only in specific at-risk subgroups of patients with sepsis and coagulation dysfunction. The definition of sepsis was recently modified, and as such, old scoring systems may no longer be appropriate for the diagnosis of sepsis-associated coagulopathy. The aim of this study was to evaluate prognostic factors in patients diagnosed with sepsis and coagulopathy according to the new sepsis definition and assess their accuracy in comparison with existing models. Retrospective analysis of the nationwide survey for recombinant human soluble thrombomodulin. General emergency and critical care centres in secondary and tertiary care hospitals. We evaluated the prognostic value of the newly proposed diagnostic criteria for sepsis-induced coagulopathy (SIC). A total of 1498 Japanese patients with sepsis and coagulopathy complications who were treated with recombinant thrombomodulin were analysed in this study. The platelet count, prothrombin time (PT) ratio, fibrinogen/fibrin degradation products, systemic inflammatory response syndrome score and Sequential Organ Failure Assessment (SOFA) score obtained just before the start of treatment were examined in relation to the 28-day mortality rate. The platelet count, PT ratio and total SOFA were independent predictors of a fatal outcome in a logistic regression model. A SIC score was defined using the three above-mentioned variables with a positivity threshold of 4 points or more. The SIC score predicted higher 28-day mortality rate compared with the current Japanese Association for Acute Medicine-disseminated intravascular coagulation score (38.4%vs34.7%). The SIC score is based on readily available parameters, is easy to calculate and has a high predictive value for 28-day mortality. Future studies are warranted to evaluate whether the SIC score may guide the decision to initiate anticoagulant therapy. © Article author(s) (or their employer(s) unless

  19. New technologies for the rapid diagnosis of neonatal sepsis.

    Science.gov (United States)

    Srinivasan, Lakshmi; Harris, Mary C

    2012-04-01

    To present recent literature on novel diagnostic tests in neonatal sepsis. Our review of technologies for the rapid diagnosis of neonatal sepsis includes new adaptations of time-honored tests as well as advances on the forefront of medicine. A recent study demonstrates that age-specific likelihood values for the complete blood count may determine risk of infection. Systematic reviews of procalcitonin, mannose-binding lectin and molecular amplification techniques provide summary data from accumulated literature on these tests. Proteomics-based and genomics-based exploratory researches suggest new combinations of markers as important signals of sepsis, whereas damage-associated molecular patterns, a class of inflammatory mediators now viewed as key players in the inflammatory cascade, may be useful predictors of disease progression and severity. Heart rate variability monitoring has also been suggested as a way to reduce mortality in very low birth weight neonates. Finally, molecular techniques are rapidly advancing in sophistication and may soon be useful as adjunctive bacterial identification tests. Several novel tests show promise in the early detection of sepsis. Highlights include new combinations of biomarkers unearthed by proteomics-based research and identification of sepsis based on gene expression profiling. Future research should focus on validation of these findings and further refinement of molecular techniques.

  20. Multi-analytical Approaches Informing the Risk of Sepsis

    Science.gov (United States)

    Gwadry-Sridhar, Femida; Lewden, Benoit; Mequanint, Selam; Bauer, Michael

    Sepsis is a significant cause of mortality and morbidity and is often associated with increased hospital resource utilization, prolonged intensive care unit (ICU) and hospital stay. The economic burden associated with sepsis is huge. With advances in medicine, there are now aggressive goal oriented treatments that can be used to help these patients. If we were able to predict which patients may be at risk for sepsis we could start treatment early and potentially reduce the risk of mortality and morbidity. Analytic methods currently used in clinical research to determine the risk of a patient developing sepsis may be further enhanced by using multi-modal analytic methods that together could be used to provide greater precision. Researchers commonly use univariate and multivariate regressions to develop predictive models. We hypothesized that such models could be enhanced by using multiple analytic methods that together could be used to provide greater insight. In this paper, we analyze data about patients with and without sepsis using a decision tree approach and a cluster analysis approach. A comparison with a regression approach shows strong similarity among variables identified, though not an exact match. We compare the variables identified by the different approaches and draw conclusions about the respective predictive capabilities,while considering their clinical significance.

  1. The Retrospective Analysis of Neonatal Sepsis Cases and Causes

    Directory of Open Access Journals (Sweden)

    Ferhan Karademir

    2009-08-01

    Full Text Available AIM: In this study we aimed to evaluate the clinical characteristics of newborns with proven sepsis, the causative agents and antibiotic resistance in our NICU. METHOD: The charts of babies with sepsis during the years 2008–2009 in our NICU were evaluated retrospectively. RESULTS: 238 hospitalized patients had 21 septic attacks. Rate of early onset septicemia was 28.5%, rate of late onset septicemia was 71.5%. 57.1% of babies with sepsis were preterm (<37 weeks. Preterm babies weighing <1500 g was %75 of all preterm babies with sepsis. The frequency of culture positive sepsis was 57.1%, 50% of these cultures were taken from blood, 41.6% from urine, 8.3% from skin swab samples. The isolated micro-organisms were coagulase-negative staphylococci (46,1%, E.coli (17,6%, Klebsiella pneumoniae (17,6%, C. Albicans (9,8% and Klebsiella oxytoca (9,8%. CONCLUSION: We think that we must consider the bacterial spectrum and their antibiotic resistance due to increase the success of the therapy. [TAF Prev Med Bull 2009; 8(4.000: 329-332

  2. Maresin 1 Mitigates Inflammatory Response and Protects Mice from Sepsis

    Directory of Open Access Journals (Sweden)

    Ruidong Li

    2016-01-01

    Full Text Available Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS. Maresin 1 (Mar1 is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and interleukin-1β (IL-1β. Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT, aspartate transaminase (AST, creatinine (Cre, and blood urea nitrogen (BUN in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation.

  3. Molecular microbiological methods in the diagnosis of neonatal sepsis

    Science.gov (United States)

    Venkatesh, Mohan; Flores, Angela; Luna, Ruth Ann; Versalovic, James

    2010-01-01

    Neonatal sepsis is a major cause of neonatal mortality and morbidity. The current gold standard for diagnosis of sepsis, namely blood culture, suffers from low sensitivity and a reporting delay of approximately 48–72 h. Rapid detection of sepsis and institution of antimicrobial therapy may improve patient outcomes. Rapid and sensitive tests that can inform clinicians regarding the institution or optimization of antimicrobial therapy are urgently needed. The ideal diagnostic test should have adequate specificity and negative predictive value to reliably exclude sepsis and avoid unnecessary antibiotic therapy. We comprehensively searched for neonatal studies that evaluated molecular methods for diagnosis of sepsis. We identified 19 studies that were assessed with respect to assay methodology and diagnostic characteristics. In addition, we also reviewed newer molecular microbiological assays of relevance that have not been fully evaluated in neonates. Molecular methods offer distinct advantages over blood cultures, including increased sensitivity and rapid diagnosis. However, diagnostic accuracy and cost–effectiveness should be established before implementation in clinical practice. PMID:20818947

  4. Novel hybrid technology for early diagnostics of sepsis

    Science.gov (United States)

    Saknite, Inga; Grabovskis, Andris; Kazune, Sigita; Rubins, Uldis; Marcinkevics, Zbignevs; Volceka, Karina; Kviesis-Kipge, Edgars; Spigulis, Janis

    2017-02-01

    Sepsis is a potentially fatal disease with mortality rate as high as 50% in patients with septic shock; mortality rate can increase by 7.6% per hour if appropriate treatment is not started. Internationally accepted guidelines for diagnosis of sepsis rely on vital sign monitoring and laboratory tests in order to recognize organ failure. This pilot study aims to explore the potential of hyperspectral and thermal imaging techniques to identify and quantify early alterations in skin oxygenation and perfusion induced by sepsis. The study comprises both physiological model experiments on healthy volunteers in a laboratory environment, as well as screening case series of patients with septic shock in the intensive care department. Hyperspectral imaging is used to determine one of the main characteristic visual signs of skin oxygenation abnormalities - skin mottling, whereas changes in peripheral perfusion have been visualized by thermal imaging as heterogeneous skin temperature areas. In order to mimic septic skin mottling in a reproducible way in laboratory environment, arterial occlusion provocation test was utilized on healthy volunteers. Visualization of oxygen saturation by hyperspectral imaging allows diagnosing microcirculatory alterations induced by sepsis earlier than visual assessment of mottling. Thermal images of sepsis patients in the clinic clearly reveal hotspots produced by perforating arteries, as well as cold regions of low blood supply. The results of this pilot study show that thermal imaging in combination with hyperspectral imaging allows the determination of oxygen supply and utilization in critically ill septic patients.

  5. Use of miRNAs as Biomarkers in Sepsis

    Directory of Open Access Journals (Sweden)

    Raluca Dumache

    2015-01-01

    Full Text Available Sepsis is one of the most common causes of death in critical patients. Severe generalized inflammation, infections, and severe physiological imbalances significantly decrease the survival rate with more than 50%. Moreover, monitoring, evaluation, and therapy management often become extremely difficult for the clinician in this type of patients. Current methods of diagnosing sepsis vary based especially on the determination of biochemical-humoral markers, such as cytokines, components of the complement, and proinflammatory and anti-inflammatory compounds. Recent studies highlight the use of new biomarkers for sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an approximate content of 19–23 nucleotides. Following biochemical and physiological imbalances, the expression of miRNAs in blood or other body fluids changes significantly. Moreover, its stability, specificity, and selectivity make miRNAs ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable species of circulating miRNAs represent potential biomarkers for monitoring the evolution of sepsis.

  6. Use of miRNAs as biomarkers in sepsis.

    Science.gov (United States)

    Dumache, Raluca; Rogobete, Alexandru Florin; Bedreag, Ovidiu Horea; Sarandan, Mirela; Cradigati, Alina Carmen; Papurica, Marius; Dumbuleu, Corina Maria; Nartita, Radu; Sandesc, Dorel

    2015-01-01

    Sepsis is one of the most common causes of death in critical patients. Severe generalized inflammation, infections, and severe physiological imbalances significantly decrease the survival rate with more than 50%. Moreover, monitoring, evaluation, and therapy management often become extremely difficult for the clinician in this type of patients. Current methods of diagnosing sepsis vary based especially on the determination of biochemical-humoral markers, such as cytokines, components of the complement, and proinflammatory and anti-inflammatory compounds. Recent studies highlight the use of new biomarkers for sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an approximate content of 19-23 nucleotides. Following biochemical and physiological imbalances, the expression of miRNAs in blood or other body fluids changes significantly. Moreover, its stability, specificity, and selectivity make miRNAs ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable species of circulating miRNAs represent potential biomarkers for monitoring the evolution of sepsis.

  7. Impaired Granuloma Formation in Sepsis: Impact of Monocytopenia.

    Science.gov (United States)

    Alingrin, Julie; Coiffard, Benjamin; Textoris, Julien; Belenotti, Pauline; Daumas, Aurélie; Leone, Marc; Mege, Jean-Louis

    2016-01-01

    Granulomas are a collection of immune cells considered to be protective in infectious diseases. The in vitro generation of granulomas is an interesting substitution to invasive approaches of granuloma study. The monitoring of immune response through the determination of in vitro granuloma formation in patients with severe sepsis may be critical to individualize treatments. We compared the in vitro generation of granulomas by co-culturing circulating mononuclear cells from 19 patients with severe sepsis, 9 patients cured from Q fever and 12 healthy subjects as controls, and Sepharose beads coated either with BCG or Coxiella burnetii extracts to analyze both immune and innate granulomas, respectively. We showed that the great majority of patients with severe sepsis were unable to form granulomas in response to BCG and C. burnetii extracts whereas more than 80% of healthy controls and patients cured from Q fever formed granulomas. We also found that monocytopenia and defective production of tumor necrosis factor were associated with reduced formation of granulomas in patients with severe sepsis even if TNF did not seem to be involved in the defective granuloma formation. Taken together, these results suggest that the deficiency of granuloma formation may be a measurement of altered recruitment and activation of monocytes and lymphocytes in patients with severe sepsis.

  8. Microglia activation in sepsis: a case-control study

    Directory of Open Access Journals (Sweden)

    Rozemuller Annemiek JM

    2007-01-01

    Full Text Available Abstract Background infection induces an acute phase response that is accompanied by non-specific symptoms collectively named sickness behavior. Recent observations suggest that microglial cells play a role in mediating behavioral changes in systemic infections. In animal models for sepsis it has been shown that after inducing lipopolysaccharide, LPS, microglia in the brain were activated. The aim of this study was to investigate whether activation of microglia can be detected in patients who died of sepsis. Methods in a case-control study brain tissue of 13 patients who died with sepsis was compared with that of 17 controls. Activated microglia were identified by expression of MHC-class II antigens and CD68. Microglia activation was analyzed by a semiquantitative score combining both the number of the immunoreactive cells and their morphology. Results in patients who died with sepsis there was a significant increase in activated microglia in the grey matter when stained with CD68 compared to controls. This effect was independent of the effect of age. Conclusion this study shows for the first time in human brain tissue an association between a systemic infection and activation of microglia in the brain. Activated microglia during sepsis could play a role in behavioral changes associated with systemic infection.

  9. Role of Pore-Forming Toxins in Neonatal Sepsis

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    Andreas F.-P. Sonnen

    2013-01-01

    Full Text Available Protein toxins are important virulence factors contributing to neonatal sepsis. The major pathogens of neonatal sepsis, group B Streptococci, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus, secrete toxins of different molecular nature, which are key for defining the disease. Amongst these toxins are pore-forming exotoxins that are expressed as soluble monomers prior to engagement of the target cell membrane with subsequent formation of an aqueous membrane pore. Membrane pore formation is not only a means for immediate lysis of the targeted cell but also a general mechanism that contributes to penetration of epithelial barriers and evasion of the immune system, thus creating survival niches for the pathogens. Pore-forming toxins, however, can also contribute to the induction of inflammation and hence to the manifestation of sepsis. Clearly, pore-forming toxins are not the sole factors that drive sepsis progression, but they often act in concert with other bacterial effectors, especially in the initial stages of neonatal sepsis manifestation.

  10. DMPD: Role of Toll-like receptor responses for sepsis pathogenesis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18086373 Role of Toll-like receptor responses for sepsis pathogenesis. Weighardt H, Holzmann B. Immunobiolog... responses for sepsis pathogenesis. Authors Weighardt H, Holzmann B. Publication Immunobiology

  11. Evaluation of culture-proven neonatal sepsis at a tertiary care ...

    African Journals Online (AJOL)

    . *Unless otherwise specified. Table 2. Organisms causing neonatal sepsis. Organism. Neonatal sepsis (N=236), n (%). EOS (N=39), n (%). LOS (N=197), n (%). Gram-positive. CONS. MRSA. Enterococcus faecalis. GBS. Enterococcus faecium.

  12. Analyzing Neutrophil Morphology, Mechanics, and Motility in Sepsis : Options and Challenges for Novel Bedside Technologies

    NARCIS (Netherlands)

    Zonneveld, Rens; Molema, Grietje; Plötz, Frans B

    Objective: Alterations in neutrophil morphology (size, shape, and composition), mechanics (deformability), and motility (chemotaxis and migration) have been observed during sepsis. We combine summarizing features of neutrophil morphology, mechanics, and motility that change during sepsis with an

  13. Prevention of Sepsis in Children: A New Paradigm for Public Policy

    Directory of Open Access Journals (Sweden)

    Carley Riley

    2012-01-01

    Full Text Available Sepsis is one of the leading causes of death worldwide. While the management of critically ill patients with sepsis is certainly better now compared to 20 years ago, sepsis-associated mortality remains unacceptably high. Annual deaths from sepsis in both children and adults far surpass the number of deaths from acute myocardial infarction (AMI, stroke, or cancer. Given the substantial toll that sepsis takes worldwide, prevention of sepsis remains a global priority. Multiple effective prevention strategies exist. Antibiotic prophylaxis, immunizations, and healthcare quality improvement initiatives are important means through which we may reduce the morbidity and mortality from sepsis around the world. Inclusion of these strategies in a coordinated and thoughtful campaign to reduce the global burden of sepsis is necessary for the improvement of pediatric health worldwide.

  14. Sepsis reconsidered: Identifying novel metrics for behavioral landscape characterization with a high-performance computing implementation of an agent-based model.

    Science.gov (United States)

    Cockrell, Chase; An, Gary

    2017-10-07

    developed two novel methods for characterizing the behavior of a RDS: Probabilistic Basins of Attraction (PBoA) and Stochastic Trajectory Analysis (STA). Computationally generated behavioral landscapes demonstrated attractor structures around stochastic regions of behavior that could be described in a complementary fashion through use of PBoA and STA. The stochasticity of the boundaries of the attractors highlights the challenge for correlative attempts to characterize and classify clinical sepsis. HPC simulations of models like the IIRABM can be used to generate approximations of the behavior space of sepsis to both establish "boundaries of futility" with respect to existing investigatory approaches and apply system engineering principles to investigate the general dynamic properties of sepsis to provide a pathway for developing control strategies. The issues that bedevil the study and treatment of sepsis, namely clinical data sparseness and inadequate experimental sampling of system behavior space, are fundamental to nearly all biomedical research, manifesting in the "Crisis of Reproducibility" at all levels. HPC-augmented simulation-based research offers an investigatory strategy more consistent with that seen in the physical sciences (which combine experiment, theory and simulation), and an opportunity to utilize the leading advances in HPC, namely deep machine learning and evolutionary computing, to form the basis of an iterative scientific process to meet the full promise of Precision Medicine (right drug, right patient, right time). Copyright © 2017. Published by Elsevier Ltd.

  15. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis

    Science.gov (United States)

    2014-01-01

    Background Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis. Methods Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored. Results Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury. Conclusions Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury. Trial registration ClinicalTrials.gov identifier NCT01434121. PMID

  16. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study.

    Science.gov (United States)

    Machado, Flavia R; Cavalcanti, Alexandre Biasi; Bozza, Fernando Augusto; Ferreira, Elaine M; Angotti Carrara, Fernanda Sousa; Sousa, Juliana Lubarino; Caixeta, Noemi; Salomao, Reinaldo; Angus, Derek C; Pontes Azevedo, Luciano Cesar

    2017-11-01

    The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4-31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8-44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2-59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02-2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37-0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9-351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the

  17. 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

  18. The new normal: immuno-modulatory agents against sepsis immune suppression

    OpenAIRE

    Hutchins, Noelle A.; Unsinger, Jacqueline; Hotchkiss, Richard S.; Ayala, Alfred

    2014-01-01

    Sepsis is the leading cause of death amongst critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the pro-inflammatory stage have failed clinically; therefore new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis...

  19. Emergency Department Management of Sepsis Patients: A Randomized, Goal-Oriented, Noninvasive Sepsis Trial.

    Science.gov (United States)

    Kuan, Win Sen; Ibrahim, Irwani; Leong, Benjamin S H; Jain, Swati; Lu, Qingshu; Cheung, Yin Bun; Mahadevan, Malcolm

    2016-03-01

    The noninvasive cardiac output monitor and passive leg-raising maneuver has been shown to be reasonably accurate in predicting fluid responsiveness in critically ill patients. We examine whether using a noninvasive protocol would result in more rapid lactate clearance after 3 hours in patients with severe sepsis and septic shock in the emergency department. In this open-label randomized controlled trial, 122 adult patients with sepsis and serum lactate concentration of greater than or equal to 3.0 mmol/L were randomized to receive usual care or intravenous fluid bolus administration guided by measurements of change of stroke volume index, using the noninvasive cardiac output monitor after passive leg-raising maneuver. The primary outcome was lactate clearance of more than 20% at 3 hours. Secondary outcomes included mortality, length of hospital and ICU stay, and total hospital cost. Analysis was intention to treat. Similar proportions of patients in the randomized intervention group (70.5%; N=61) versus control group (73.8%; N=61) achieved the primary outcome, with a relative risk of 0.96 (95% confidence interval [CI] 0.77 to 1.19). Secondary outcomes were similar in both groups (P>.05 for all comparisons). Hospital mortality occurred in 6 patients (9.8%) each in the intervention and control groups on or before 28 days (relative risk=1.00; 95% CI 0.34 to 2.93). Among a subgroup of patients with underlying fluid overload states, those in the intervention group tended to receive clinically significantly more intravenous fluids at 3 hours (difference=975 mL; 95% CI -450 to 1,725 mL) and attained better lactate clearance (difference=19.7%; 95% CI -34.6% to 60.2%) compared with the control group, with shorter hospital lengths of stay (difference=-4.5 days; 95% CI -9.5 to 2.5 days). Protocol-based fluid resuscitation of patients with severe sepsis and septic shock with the noninvasive cardiac output monitor and passive leg-raising maneuver did not result in better

  20. Manipulation of the Complement System for Benefit in Sepsis

    Directory of Open Access Journals (Sweden)

    Peter A. Ward

    2012-01-01

    Full Text Available There is evidence in sepsis, both in rodents and in humans, that activation of the complement system results in excessive production of C5a, which triggers a series of events leading to septic shock, multiorgan failure, and lethality. In rodents following cecal ligation and puncture (CLP, which induces polymicrobial sepsis, in vivo blockade of C5a using neutralizing antibodies dramatically improved survival, reduced apoptosis of lymphoid cells, and attenuated the ensuing coagulopathy. Based on these data, it seems reasonable to consider therapeutic blockade of C5a in humans entering into sepsis and septic shock. Strategies for the development of such an antibody for use in humans are presented.

  1. Streptococcus pneumoniae: the forgotten microorganism in neonatal sepsis.

    Science.gov (United States)

    Rodriguez, Beatriz Fernandez; Mascaraque, Luis Rubio; Fraile, Leticia Ruiz; Perez, Irene Cuadrado; Kuder, Krzysztof

    2015-06-01

    Streptococcus pneumoniae is a rarely cause of neonatal sepsis. Its prevalence is low but with a mortality of 50%. Measures to prevent Streptococcus agalactiae transmission could help to increase Invasive Pneumococcal Disease (IPD) in newborns. Transmission could be from mother intrapartum; or in those cases of late onset sepsis, the community carriers. Systematic vaccination with PCV-7 and PCV-13 has reduced IPD rates. We present a case of a newborn with no perinatal risk factors for infection. In the first 24 hours after surgery of an ovarian cyst, the patient started with bad general condition with fever and regular perfusion. Empiric antibiotic treatment was started. Streptococcus pneumoniae was isolated in blood culture. In neonatal sepsis, we always think in Streptococcus agalactiae. Streptococcus pneumoniae is rare but with a high morbidity and mortality. Systematic vaccination is a measure that has demonstrated a reduction in the incidence of Invasive pneumococcal disease.

  2. Intracranial Pressure during HighVolume Hemofiltration in Severe Sepsis

    Directory of Open Access Journals (Sweden)

    A. P. Berdnikov

    2014-01-01

    Full Text Available Objective: to define the prognostic value of intracranial pressure (ICP changes in highvolume hemofiltration (HVHF in patients with severe sepsis and normal preperfusion ICP.Subjects and methods. A retrospective study was conducted in 50 patients (a total of 134 sessions with severe sepsis and normal baseline ICP who received ther apy using HVHF for extrarenal indications. Based on ICP changes before and after HVHF, the investigators identified 2 groups: 1 no ICP changes (n=81; 2 elevated ICP (n=53.Conclusion. HVHF is ineffective when the normal preperfusion ICP is increased in patients with severe sepsis who have a concurrence of an arteriovenous carbon dioxide difference of more than 8 mm Hg and a Glasgow coma score of less than 10.

  3. The coagulopathy in sepsis: significance and implications for treatment

    Directory of Open Access Journals (Sweden)

    Berardino Pollio

    2011-09-01

    Full Text Available Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC. There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant system, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.

  4. Risk factors for neonatal sepsis and perinatal death among infants enrolled in the prevention of perinatal sepsis trial, Soweto, South Africa.

    Science.gov (United States)

    Schrag, Stephanie J; Cutland, Clare L; Zell, Elizabeth R; Kuwanda, Locadiah; Buchmann, Eckhart J; Velaphi, Sithembiso C; Groome, Michelle J; Madhi, Shabir A

    2012-08-01

    Factors associated with neonatal sepsis, an important cause of child mortality, are poorly described in Africa. We characterized factors associated with early-onset (days 0-2 of life) and late-onset (days 3-28) -sepsis and perinatal death among infants enrolled in the Prevention of Perinatal Sepsis Trial (NCT00136370 at ClinicalTrials.gov), Soweto, South Africa. Secondary analysis of 8011 enrolled mothers and their neonates. Prenatal and labor records were abstracted and neonatal wards were monitored for hospitalized Prevention of Perinatal Sepsis-enrolled neonates. Endpoint definitions required clinical and laboratory signs. All univariate factors associated with endpoints at P perinatal period. Factors associated with early-onset sepsis included preterm delivery [adjusted relative risk (aRR) = 2.6; 95% confidence interval (CI): 1.4-4.8]; low birth weight (perinatal death and culture-confirmed sepsis. MSAF (aRR = 2.4, 95% CI: 1.1-5.0) was associated with late-onset sepsis. Preterm and low birth weight were important sepsis risk factors. MSAF and first birth were also associated with sepsis and death, warranting further exploration. Intrapartum antibiotic prophylaxis did not protect against all-cause sepsis or death, underscoring the need for alternate prevention strategies.

  5. INTERPRETATION OF HAEMATOLOGICAL PARAMETERS IN NEONATES AT RISK FOR SEPSIS

    Directory of Open Access Journals (Sweden)

    Kajal Basavaraj Punyashetty

    2016-06-01

    Full Text Available BACKGROUND Neonates are uniquely susceptible to overwhelming bacterial infections. It is very essential to diagnose the sepsis in early phase and it is also important to rule out sepsis to prevent irrational use of antibiotics. Though blood culture is considered as gold standard, it is time consuming with limitation in preterm and has high false negative rates. For the same reason, several rapid haematological tests are done as part of sepsis screen for early diagnosis of neonatal sepsis. OBJECTIVE The study was done to establish the role of haematological parameters like Total Leucocyte Count (TLC, Absolute Neutrophil Count (ANC, Immature to Total Neutrophil ratio (I/T ratio, Platelet count, C – Reactive Protein (CRP, Micro-Erythrocyte Sedimentation Rate (m-ESR, either alone or in combination as reliable indicators of septicaemia in clinically suspected neonates. METHODS A prospective study of 100 neonates clinically suspected as having sepsis, who were admitted to NICU, Navodaya Medical College, Hospital and Research Centre, Raichur were included. The above haematological parameters were evaluated and statistically analysed. RESULTS Among 100 neonates, only 42 cases were positive for blood culture and were considered true positives. Haematological parameters like TLC, I/T ratio, CRP showed high sensitivity, specificity, positive predictive value and negative predictive value as individually or in combination. ANC and micro-ESR showed low sensitivity but high specificity. Results were promising when tests were done in combination using haematological scoring system. CONCLUSION Irrespective of blood culture-positivity, evaluation of haematological parameters aid in early diagnosis and provide a rational basis for therapy and management of neonatal sepsis.

  6. Immunomodulatory intervention with Gamma interferon in mice with sepsis.

    Science.gov (United States)

    Wang, Yu; Kong, Bing-Bing; Yang, Wen-Ping; Zhao, Xin; Zhang, Rong

    2017-09-15

    Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pretreated with recombinant human IFNg (0.01μg/g of body weight) before CLP. The immunophenotyping of cell surface receptor expression, and regulatory T cells (CD4+CD25+Foxp3+) were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of IFNg and interleukin 4 (IL-4) in the spleen and plasma levels of TNF-α, IL-6, high-mobility group box 1 (HMGB1) were determined using enzyme-linked immunosorbent assay. IFNg markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNg-treated mices had significantly decreased percentages of programmed cell death 1 (PD-1) receptors, increased the percentages of positive costimulatory receptor CD28 on CD4 T cells expressing. IFNg markedly reduced T-cell apoptosis through upregulating the expression of Bcl-2. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNg -treated mices. Moreover, IFNg treatment reduced plasma levels of TNF-α, IL-6, HMGB1. IFNg can be a powerful regulator of immune function under sepsis conditions. Therefore, targeted immune-enhancement with IFNg may be a valid therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Distribution characteristics of liquid sequestration in rats with sepsis

    Directory of Open Access Journals (Sweden)

    Bin LI

    2012-03-01

    Full Text Available Objective To investigate the distribution characteristics of organs with liquid sequestration during fluid resuscitation in rats with sepsis. Methods Fifty male Wistar rats were randomly divided into five groups: control group (n=10, sepsis group (n=10, crystalloid group (n=10, albumin group (n=10, and artificial colloid (HAES group (n=10. The sepsis model was reproduced by cecal ligation and puncture. The mean arterial pressure was monitored with carotid artery intubation. Twelve hours after fluid infusion by micro-infusion pump via the femoral vein, tissues from the heart, liver, lungs, kidney (right, and small intestine were harvested to observe the pathological changes and calculate the tissue water content. Results The water content of every visceral tissue was higher in the sepsis group than in the control group (P < 0.05; the water content in the heart, liver, and lung tissues was higher in the albumin group than in the crystalloid group (P < 0.05. The water content in both albumin and crystalloid groups was higher than that in the sepsis group (P < 0.05. Moreover, the water content in the heart, liver, and lungs in the HAES group was lower than that in the crystalloid and albumin groups (P < 0.05. Cellular injuries were more severe in the heart, liver, and lungs than in the intestine and kidney in the crystalloid group and albumin group under electron-microscope. Conclusion Liquid sequestration exists mainly in the lungs, heart, and liver of rats with sepsis during fluid resuscitation. The phenomenon is less evident in the kidney and small intestine. Artificial colloid can reduce capillary leak with a good volume expansion effect.

  8. Optical detection of sepsis markers using liquid crystal based biosensors

    Science.gov (United States)

    McCamley, Maureen K.; Artenstein, Andrew W.; Opal, Steven M.; Crawford, Gregory P.

    2007-02-01

    A liquid crystal based biosensor for the detection and diagnosis of sepsis is currently in development. Sepsis, a major clinical syndrome with a significant public health burden in the US due to a large elderly population, is the systemic response of the body to a localized infection and is defined as the combination of pathologic infection and physiological changes. Bacterial infections are responsible for 90% of cases of sepsis in the US. Currently there is no bedside diagnostic available to positively identify sepsis. The basic detection scheme employed in a liquid crystal biosensor contains attributes that would find value in a clinical setting, especially for the early detection of sepsis. Utilizing the unique properties of liquid crystals, such as birefringence, a bedside diagnostic is in development which will optically report the presence of biomolecules. In a septic patient, an endotoxin known as lipopolysaccharide (LPS) is released from the outer membrane of Gram-negative bacteria and can be found in the blood stream. It is hypothesized that this long chained molecule will cause local disruptions to the open surface of a sensor containing aligned liquid crystal. The bulk liquid crystal ampli.es these local changes at the surface due to the presence of the sepsis marker, providing an optical readout through polarizing microscopy images. Liquid crystal sensors consisting of both square and circular grids, 100-200 μm in size, have been fabricated and filled with a common liquid crystal material, 5CB. Homeotropic alignment was confirmed using polarizing microscopy. The grids were then contacted with either saline only (control), or saline with varying concentrations of LPS. Changes in the con.guration of the nematic director of the liquid crystal were observed through the range of concentrations tested (5mg/mL - 1pg/mL) which have been confirmed by a consulting physician as clinically relevant levels.

  9. Endocan is useful biomarker of survival and severity in sepsis.

    Science.gov (United States)

    Mihajlovic, Dunja M; Lendak, Dajana F; Brkic, Snezana V; Draskovic, Biljana G; Mitic, Gorana P; Novakov Mikic, Aleksandra S; Cebovic, Tatjana N

    2014-05-01

    Coagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined. 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Patients were categorized in two groups according to sepsis severity and organ failure and MODS development was assessed in the first 48 h from ICU admission. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and endothelial cell specific molecule-1(endocan) levels, as well as procalcitonin (PCT) and C-reactive protein (CRP) were determined within the first 24h of the onset of the disease. Predictive APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores were calculated on the day of ICU admission. Data were used to determine an association between day 1 biomarker levels, organ dysfunction score values and the development of organ failure, multiple organ dysfunction syndrome (MODS), and mortality during 28 days. These connections were determined by plotting of receiver operating characteristic (ROC) curves. Differences between groups were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test. Concentration of endocan was significantly higher in the group of patients with sepsis induced organ failure, MODS development and in the group of non- survivors in contrast to group with less severe form of the disease, without multiorgan failure, and in contrast to group of survivors (pAPACHE II (AUC:0.55) and SOFA (AUC: 0.57) scores for organ failure. Results of our study show that endocan can be used as strong and significant predictor of sepsis severity and outcome, perhaps even better than SOFA and APACHE II scores. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis.

    Directory of Open Access Journals (Sweden)

    Li Qin

    2017-02-01

    Full Text Available Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally "unintended" interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches.

  11. Potentially modifiable factors contributing to sepsis-associated encephalopathy.

    Science.gov (United States)

    Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

    2017-08-01

    Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia 10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

  12. The etiology and outcome of adult patients presenting with sepsis to ...

    African Journals Online (AJOL)

    Background: Sepsis accounts for a significant burden of morbidity and mortality. In developed world, it is implicated as the second leading cause of non-cardiac death. Mortality from sepsis is on the increase with a mortality rate of 33-61%. In spite of the high burden of sepsis in sub Saharan Africa, data regarding the etiology ...

  13. Sepsis in the intensive care unit: epidemiology, outcome and host response

    NARCIS (Netherlands)

    van Vught, L.A.

    2016-01-01

    Sepsis is a life-threatening syndrome that arises when a dysbalanced patient response to an infection causes damage to the body’s own organs and tissues. Sepsis is, to date, still a major cause of morbidity and mortality worldwide. A detailed understanding of the pathogenesis of sepsis is likely to

  14. Modulation of innate immune responses in the treatment of sepsis and pneumonia

    NARCIS (Netherlands)

    Schultz, Marcus J.; van der Poll, Tom

    2004-01-01

    In the last decades several preclinical models for sepsis have been used to study the pathophysiologic processes during sepsis. Although these studies revealed promising immunomodulating agents for the treatment of sepsis, clinical trials evaluating the efficacy of these new agents in septic

  15. The Impact of HIV Co-Infection on the Genomic Response to Sepsis

    NARCIS (Netherlands)

    Huson, Michaëla A. M.; Scicluna, Brendon P.; van Vught, Lonneke A.; Wiewel, Maryse A.; Hoogendijk, Arie J.; Cremer, Olaf L.; Bonten, Marc J. M.; Schultz, Marcus J.; Franitza, Marek; Toliat, Mohammad R.; Nürnberg, Peter; Grobusch, Martin P.; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection

  16. Characteristics of early-onset neonatal sepsis caused by Escherichia coli

    Directory of Open Access Journals (Sweden)

    Chin-Han Tsai

    2012-03-01

    Conclusion: Early-onset E coli sepsis is more common in premature and very low birth weight infants and is more likely associated with intrapartum fever, PPROM, and sepsis onset on the first day of life than non-E coli sepsis. Broad-spectrum, multiple antibiotics or longer duration of antibiotic exposure may be associated with antibiotic-resistant pathogen infection.

  17. Is there NO treatment for severe sepsis? | Bredan | Libyan Journal of ...

    African Journals Online (AJOL)

    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, ...

  18. Critical care management of severe sepsis and septic shock: a cost-analysis

    NARCIS (Netherlands)

    Koster-Brouwer, Maria E; Klein Klouwenberg, Peter M C|info:eu-repo/dai/nl/33706864X; Pasma, Wietze; Bosmans, Judith E; van der Poll, Tom; Bonten, Marc J M|info:eu-repo/dai/nl/123144337; Cremer, Olaf L|info:eu-repo/dai/nl/304815683

    2016-01-01

    Background Sepsis treatment has been associated with high costs. Furthermore, both the incidence of sepsis and the severity of illness at presentation appear to be increasing. We estimated healthcare costs related to the treatment of patients with sepsis in the intensive care unit (ICU) and aimed to

  19. Fatal sepsis caused by an unusual Klebsiella species that was misidentified by an automated identification system.

    Science.gov (United States)

    Seki, Masafumi; Gotoh, Kazuyoshi; Nakamura, Shota; Akeda, Yukihiro; Yoshii, Tadashi; Miyaguchi, Shinichi; Inohara, Hidenori; Horii, Toshihiro; Oishi, Kazunori; Iida, Tetsuya; Tomono, Kazunori

    2013-05-01

    This is a description of fatal sepsis caused by infection with Klebsiella variicola, which is an isolate genetically related to Klebsiella pneumoniae. The patient's condition was incorrectly diagnosed as common sepsis caused by K. pneumoniae, which was identified using an automated identification system, but next-generation sequencing and the non-fermentation of adonitol finally identified the cause of sepsis as K. variicola.

  20. Voluntary running exercise protects against sepsis-induced early inflammatory and pro-coagulant responses in aged mice.

    Science.gov (United States)

    Tyml, Karel; Swarbreck, Scott; Pape, Cynthia; Secor, Dan; Koropatnick, James; Feng, Qingping; Veldhuizen, Ruud A W; Gill, Sean E

    2017-08-08

    Despite many animal studies and clinical trials, mortality in sepsis remains high. This may be due to the fact that most experimental studies of sepsis employ young animals, whereas the majority of septic patients are elderly (60 - 70 years). The objective of the present study was to examine the sepsis-induced inflammatory and pro-coagulant responses in aged mice. Since running exercise protects against a variety of diseases, we also examined the effect of voluntary running on septic responses in aged mice. Male C57BL/6 mice were housed in our institute from 2-3 to 22 months (an age mimicking that of the elderly). Mice were prevented from becoming obese by food restriction (given 70-90% of ad libitum consumption amount). Between 20 and 22 months, a subgroup of mice ran voluntarily on wheels, alternating 1-3 days of running with 1-2 days of rest. At 22 months, mice were intraperitoneally injected with sterile saline (control) or 3.75 g/kg fecal slurry (septic). At 7 h post injection, we examined (1) neutrophil influx in the lung and liver by measuring myeloperoxidase and/or neutrophil elastase in the tissue homogenates by spectrophotometry, (2) interleukin 6 (IL6) and KC in the lung lavage by ELISA, (3) pulmonary surfactant function by measuring percentage of large aggregates, (4) capillary plugging (pro-coagulant response) in skeletal muscle by intravital microscopy, (5) endothelial nitric oxide synthase (eNOS) protein in skeletal muscle (eNOS-derived NO is putative inhibitor of capillary plugging) by immunoblotting, and (6) systemic blood platelet counts by hemocytometry. Sepsis caused high levels of pulmonary myeloperoxidase, elastase, IL6, KC, liver myeloperoxidase, and capillary plugging. Sepsis also caused low levels of surfactant function and platelet counts. Running exercise increased eNOS protein and attenuated the septic responses. Voluntary running protects against exacerbated sepsis-induced inflammatory and pro-coagulant responses in aged mice

  1. Towards a consensus definition of maternal sepsis: results of a systematic review and expert consultation.

    Science.gov (United States)

    Bonet, Mercedes; Nogueira Pileggi, Vicky; Rijken, Marcus J; Coomarasamy, Arri; Lissauer, David; Souza, João Paulo; Gülmezoglu, Ahmet Metin

    2017-05-30

    There is a need for a clear and actionable definition of maternal sepsis, in order to better assess the burden of this condition, trigger timely and effective treatment and allow comparisons across facilities and countries. The objective of this study was to review maternal sepsis definitions and identification criteria and to report on the results of an expert consultation to develop a new international definition of maternal sepsis. All original and review articles and WHO documents, as well as clinical guidelines providing definitions and/or identification criteria of maternal sepsis were included. A multidisciplinary international panel of experts was surveyed through an online consultation in March-April 2016 on their opinion on the existing sepsis definitions, including new definition of sepsis proposed for the adult population (2016 Third International Consensus Definitions for Sepsis and Septic Shock) and importance of different criteria for identification of maternal sepsis. The definition was agreed using an iterative process in an expert face-to-face consensus development meeting convened by WHO and Jhpiego. Standardizing the definition of maternal sepsis and aligning it with the current understanding of sepsis in the adult population was considered a mandatory step to improve the assessment of the burden of maternal sepsis by the expert panel. The literature review and expert consultation resulted in a new WHO consensus definition "Maternal sepsis is a life-threatening condition defined as organ dysfunction resulting from infection during pregnancy, child-birth, post-abortion, or post-partum period". Plans are in progress to validate the new WHO definition of maternal sepsis in a large international population. The operationalization of the new maternal sepsis definition requires generation of a set of practical criteria to identify women with sepsis. These criteria should enable clinicians to focus on the timely initiation of actionable elements of

  2. Flunarizine suppresses endothelial Angiopoietin-2 in a calcium - dependent fashion in sepsis.

    Science.gov (United States)

    Retzlaff, Jennifer; Thamm, Kristina; Ghosh, Chandra C; Ziegler, Wolfgang; Haller, Hermann; Parikh, Samir M; David, Sascha

    2017-03-09

    Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection leading to systemic inflammation and endothelial barrier breakdown. The vascular-destabilizing factor Angiopoietin-2 (Angpt-2) has been implicated in these processes in humans. Here we screened in an unbiased approach FDA-approved compounds with respect to Angpt-2 suppression in endothelial cells (ECs) in vitro. We identified Flunarizine - a well-known anti-migraine calcium channel (CC) blocker - being able to diminish intracellular Angpt-2 protein in a time- and dose-dependent fashion thereby indirectly reducing the released protein. Moreover, Flunarizine protected ECs from TNFα-induced increase in Angpt-2 transcription and vascular barrier breakdown. Mechanistically, we could exclude canonical Tie2 signalling being responsible but found that three structurally distinct T-type - but not L-type - CC blockers can suppress Angpt-2. Most importantly, experimental increase in intracellular calcium abolished Flunarizine's effect. Flunarizine was also able to block the injurious increase of Angpt-2 in murine endotoxemia in vivo. This resulted in reduced pulmonary adhesion molecule expression (intercellular adhesion molecule-1) and tissue infiltration of inflammatory cells (Gr-1). Our finding could have therapeutic implications as side effects of Flunarizine are low and specific sepsis therapeutics that target the dysregulated host response are highly desirable.

  3. Intermediate-term and long-term mortality among acute medical patients hospitalized with community-acquired sepsis

    DEFF Research Database (Denmark)

    Henriksen, Daniel P; Pottegård, Anton; Laursen, Christian B

    2017-01-01

    .5%) presented with severe sepsis, and 21 (1.2%) presented with septic shock. Thirty-day all-cause mortality for patients with sepsis, severe sepsis, and septic shock was 6.1, 18.8, and 38.1%, respectively. The adjusted HR among patients with sepsis of any severity within the time periods 31-180, 181-365, 366...

  4. Gentamicin resistance among Escherichia coli strains isolated in neonatal sepsis.

    Science.gov (United States)

    Hasvold, J; Bradford, L; Nelson, C; Harrison, C; Attar, M; Stillwell, T

    2013-01-01

    Neonatal sepsis is a significant cause of morbidity and mortality among term and preterm infants. Ampicillin and gentamicin are standard empiric therapy for early onset sepsis. Four cases of neonatal sepsis secondary to Escherichia coli (E. coli) found to be gentamicin resistant occurred within a five week period in one neonatal intensive care unit (NICU). To determine whether these cases could be tied to a single vector of transmission, and to more broadly evaluate the incidence of gentamicin resistant strains of E. coli in the neonatal population at our institution compared to other centers, we reviewed the charts of the four neonates (Infants A through D) and their mothers. The E. coli isolates were sent for Pulse Field Gel Electrophoresis (PFGE) to evaluate for genetic similarity between strains. We also reviewed all positive E. coli cultures from one NICU over a two year period. Infants A and B had genetically indistinguishable strains which matched that of urine and placental cultures of Infant B's mother. Infant C had a genetically distinct organism. Infant D, the identical twin of Infant C, did not have typing performed. Review of all cultures positive for E. coli at our institution showed a 12.9 percent incidence of gentamicin-resistance. A review of other studies showed that rates of resistance vary considerably by institution. We conclude that gentamicin-resistant E. coli is a relatively uncommon cause of neonatal sepsis, but should remain a consideration in patients who deteriorate despite initiation of empiric antibiotics.

  5. Predicting and managing sepsis in burn patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Nunez Lopez O

    2017-08-01

    Full Text Available Omar Nunez Lopez,1,2 Janos Cambiaso-Daniel,1–3 Ludwik K Branski,1,2 William B Norbury,1,2 David N Herndon1,2,4 1Department of Surgery, University of Texas Medical Branch, 2Shriners Hospitals for Children, Galveston, TX, USA; 3Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria; 4Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA Abstract: Modern burn care has led to unprecedented survival rates in burn patients whose injuries were fatal a few decades ago. Along with improved survival, new challenges have emerged in the management of burn patients. Infections top the list of the most common complication after burns, and sepsis is the leading cause of death in both adult and pediatric burn patients. The diagnosis and management of sepsis in burns is complex as a tremendous hypermetabolic response secondary to burn injury can be superimposed on systemic infection, leading to organ dysfunction. The management of a septic burn patient represents a challenging scenario that is commonly encountered by providers caring for burn patients despite preventive efforts. Here, we discuss the current perspectives in the diagnosis and treatment of sepsis and septic shock in burn patients. Keywords: burn injury, thermal injury, burn sepsis, procalcitonin, antibiotics, biomarkers, cytokines

  6. 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.

  7. Leptin Exacerbates Sepsis-Mediated Morbidity and Mortality

    Science.gov (United States)

    Shapiro, Nathan I.; Khankin, Eliyahu V.; Van Meurs, Matijs; Shih, Shou-Ching; Lu, Shulin; Yano, Midori; Castro, Pedro R.; Maratos-Flier, Eleftheria; Parikh, Samir M.; Karumanchi, S. Ananth; Yano, Kiichiro

    2011-01-01

    The adipose-derived hormone leptin is well known for its contribution to energy metabolism and satiety signaling in the hypothalamus. Previous studies suggested that obesity is an independent risk factor for sepsis morbidity and mortality, and it is associated with elevated baseline levels of circulating leptin in normal, nonseptic patients. In mouse endotoxemia and cecal ligation puncture models of sepsis, we observed elevated levels of leptin and soluble leptin receptor (sLR). Exogenously administered leptin increased mortality in endotoxemia and cecal ligation puncture models and was associated with increased expression of adhesion and coagulation molecules, macrophage infiltration into the liver and kidney, and endothelial barrier dysfunction. Conversely, longform leptin receptor-deficient mice were protected from sepsis morbidity and mortality and had less endothelial dysfunction. Furthermore, an in vitro study revealed that leptin-induced endothelial dysfunction is likely mediated, at least in part, by monocytes. Moreover, administration of an sLR conferred a survival benefit. Human septic patients have increased circulating sLR concentrations, which were correlated with disease severity indices. Together, these data support a pathogenic role for leptin signaling during sepsis. PMID:20519646

  8. Role of apolipoprotein CI in lipid metabolism and bacterial sepsis

    NARCIS (Netherlands)

    Berbée, Jimmy Fransiscus Paulus

    2007-01-01

    The research described in this thesis focussed on the role of apolipoproteins in lipid metabolism, inflammation and bacterial sepsis, with specific emphasis on apoCI. From studies in human APOC1¬-transgenic and apoc1-/- mice, we were able to identify apoCI as a potent inhibitor of triglyceride

  9. Sensitivity pattern of bacterial isolates in childhood sepsis in clinical ...

    African Journals Online (AJOL)

    To determine the commonest organism cultured from the blood of children suspected to have bacterial sepsis and their antibiogram sensitivity using the commonly used antibiotics in a private practice and see if there are differences from established data from other areas. Children beyond neonatal age presenting to a ...

  10. The Resistable Rise of Surgical Sepsis in Malawi | Lavy | Malawi ...

    African Journals Online (AJOL)

    The Resistable Rise of Surgical Sepsis in Malawi. C Lavy, C Schmidt, E Kalau, J Phuka. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about ...

  11. 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...

  12. Bacteriological profile in neonatal sepsis at the University teaching ...

    African Journals Online (AJOL)

    Infections are the biggest cause of neonatal deaths in developing countries and most of them can be preventable. Predominant causative bacterial agents kept changing overtime as such, this retrospective cross sectional study was designed to determine the bacteriological profile in neonatal sepsis and their susceptibilty to ...

  13. Arginine, citrulline and nitric oxide metabolism in sepsis

    Science.gov (United States)

    Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

  14. Prevalence Of Early Onset Sepsis In Relation To Exclusive Breast ...

    African Journals Online (AJOL)

    Neonatal Septicaemia (NNS) remains an important cause of morbidity and mortality in Nigeria. This prospective cross- sectional study was carried out to determine the relationship between exclusive breastfeeding and incidence and outcome of neonatal sepsis in population of Nigerian newborns. Subjects were babies ...

  15. Salmonella sepsis in African children | Graham | Malawi Medical ...

    African Journals Online (AJOL)

    Salmonella sepsis in African children. SM Graham. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's ...

  16. Neutrophil CD64 in early-onset neonatal sepsis

    African Journals Online (AJOL)

    EL-HAKIM

    Gonzalez BE, Mercado CK, Johnson L,. Brodsky NL, Bhandari V. Early markers of late- onset sepsis in premature neonates: clinical, hematological and cytokine profile. J Perinat Med. 2003; 31: 60 –8. 6. Ng PC. Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed 2004; 89: F229-. 35. 7. Ng PC, Lam ...

  17. Clinical Decision Support for Early Recognition of Sepsis.

    Science.gov (United States)

    Amland, Robert C; Hahn-Cover, Kristin E

    2016-01-01

    Sepsis is an inflammatory response triggered by infection, with a high in-hospital mortality rate. Early recognition and treatment can reverse the inflammatory response, with evidence of improved patient outcomes. One challenge clinicians face is identifying the inflammatory syndrome against the background of the patient's infectious illness and comorbidities. An approach to this problem is implementation of computerized early warning tools for sepsis. This multicenter retrospective study sought to determine clinimetric performance of a cloud-based computerized sepsis clinical decision support system (CDS), understand the epidemiology of sepsis, and identify opportunities for quality improvement. Data encompassed 6200 adult hospitalizations from 2012 through 2013. Of 13% patients screened-in, 51% were already suspected to have an infection when the system activated. This study focused on a patient cohort screened-in before infection was suspected; median time from arrival to CDS activation was 3.5 hours, and system activation to diagnostic collect was another 8.6 hours. © The Author(s) 2014.

  18. Sepsis Patient Detection and Monitor Based on Auto-BN.

    Science.gov (United States)

    Jiang, Yu; Sha, Lui; Rahmaniheris, Maryam; Wan, Binhua; Hosseini, Mohammad; Tan, Pengliu; Berlin, Richard B

    2016-04-01

    Sepsis is a life-threatening condition caused by an inappropriate immune response to infection, and is a leading cause of elderly death globally. Early recognition of patients and timely antibiotic therapy based on guidelines improve survival rate. Unfortunately, for those patients, it is often detected late because it is too expensive and impractical to perform frequent monitoring for all the elderly. In this paper, we present a risk driven sepsis screening and monitoring framework to shorten the time of onset detection without frequent monitoring of all the elderly. Within this framework, the sepsis ultimate risk of onset probability and mortality is calculated based on a novel temporal probabilistic model named Auto-BN, which consists of time dependent state, state dependent property, and state dependent inference structures. Then, different stages of a patient are encoded into different states, monitoring frequency is encoded into the state dependent property, and screening content is encoded into different state dependent inference structures. In this way, the screening and monitoring frequency and content can be automatically adjusted when encoding the sepsis ultimate risk into the guard of state transition. This allows for flexible manipulation of the tradeoff between screening accuracy and frequency. We evaluate its effectiveness through empirical study, and incorporate it into existing medical guidance system to improve medical healthcare.

  19. Gene Expression Profiling of Apoptosis Regulators in Patients with Sepsis

    NARCIS (Netherlands)

    Hoogerwerf, Jacobien J.; van Zoelen, Marieke A.; Wiersinga, W. Joost; van 't Veer, Cornelis; de Vos, Alex F.; de Boer, Anita; Schultz, Marcus J.; Hooibrink, Berend; de Jonge, Evert; van der Poll, Tom

    2010-01-01

    Introduction: Sepsis is associated with a dysregulation of apoptosis in immune cells, which has been implicated in both immunosuppression and multiple organ failure. We describe the expression profiles of genes encoding key regulators of apoptosis in highly purified monocytes, granulocytes and CD4+

  20. Immunomodulatory Effect of Continuous Venovenous Hemofiltration during Sepsis: Preliminary Data

    Directory of Open Access Journals (Sweden)

    Giuseppe Servillo

    2013-01-01

    Full Text Available Introduction. Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS, which is the most frequent cause of death in intensive care unit patients. Many pro- and anti-inflammatory mediators, such as interleukin-6 (IL-6, play a strategic role in septic syndrome. Continuous renal replacement therapy (CRRT removes in a nonselective way pro- and anti-inflammatory mediators. Objective. To investigate the effects of continuous venovenous hemofiltration (CVVH as an immunomodulatory treatment of sepsis in a prospective clinical study. Methods. High flux hemofiltration (Qf = 60 ml/Kg/hr was performed for 72 hr in thirteen critically ill patients suffering from severe sepsis or septic shock with acute renal failure (ARF. IL-6 gene expression was measured by real-time PCR analysis on RNA extracted from peripheral blood mononuclear cell before beginning of treatment (T0 and after 12, 24, 48, and 72 hours (T1–4. Results. Real-time PCR analysis demonstrated in twelve patients IL-6 mRNA reduction after 12 hours of treatment and a progressive increase after 24, 48, and 72 hours. Conclusions. We suggest that an immunomodulatory effect might exist during CVVH performed in critically ill patients with severe sepsis and septic shock. Our data show that the transcriptional activity of IL-6 increases during CVVH.

  1. The Surviving Sepsis Campaign: a history and a perspective.

    Science.gov (United States)

    Marshall, John C; Dellinger, R Phillip; Levy, Mitchell

    2010-06-01

    The Surviving Sepsis Campaign (SSC) was launched in 2002 as a collaborative initiative of the European Society of Intensive Care Medicine (ESICM), the International Sepsis Forum (ISF), and the Society of Critical Care Medicine (SCCM). Its objective was, through the development and promulgation of evidence-based guidelines that facilitated the application of knowledge derived from clinical trials to bedside practice, to effect a 25% reduction in the relative risk of death from severe sepsis and septic shock. The evolution and content of the SSC is summarized and the scientific basis of the conclusions is reviewed from the literature. The SSC developed evidence-based management guidelines and undertook a broad educational program to implement them by integrating their recommendations into resuscitation and management bundles. The process engaged practitioners in North America, Europe, and South America and was supported by professional societies around the world. It also engendered controversy based on accusations of undue industry influence and some dissatisfaction among individuals who were antagonistic toward protocolization of care. By its conclusion, more than 22,000 patients with sepsis had been entered in the SSC database, and analysis of the results showed that participation in the SSC was associated with a 5.4% absolute survival benefit. The SSC has impacted the care of septic patients and catalyzed changes that are likely to persist and evolve.

  2. Surviving Sepsis Puerto Rico: A Call For Action.

    Science.gov (United States)

    Vigo, Ronald; Matos, Miguel Laforet; Turbay, Tamid

    2015-01-01

    There are 1.7 million sepsis-related hospitalizations each year making it the sixth most common cause for hospitalization in the United States. Not only are this hospitalizations common, they are expensive to our medical system with $15.3 billion spent yearly (3) and hospitalizations lasting 75% longer than for other conditions. In 2001, Rivers et al published in the NEJM the results of his study "Early Goal Directed Therapy (EGDT) in The Treatment of Severe Sepsis and Septic Shock". EGDT demonstrated a 16.5% decrease in mortality in septic patients (4). In 2002 the Surviving Sepsis Campaign began as a collaboration between the Society of Critical Care Medicine and European Society of Intensive Care Medicine with goals of reducing worldwide sepsis related mortality by 25% in the next 5 years. Despite the proven benefit of early identification and management, knowledge regarding the topic in Puerto Rico remains scarce. In a study performed in PR by Fernandez et al. in 2006, only an alarming 31.4% of doctors from different specialties correctly identified SIRS criteria. Our goal is to educate physicians about the importance of early identification and treatment of the septic patient. A campaign to increase awareness and improve care is essential and we propose treatment protocols for our Puerto Rican hospitals to help reduce morbidity, mortality, length of stay and costs.

  3. Sepsis de origen infrecuente en una mujer anciana

    Directory of Open Access Journals (Sweden)

    Ana Mateos Diaz

    2014-06-01

    Full Text Available Mujer de 85 años con antecedentes de diabetes mellitus tipo 2 y neoplasia de colon intervenida hace3 años. Ingresa por un cuadro febril sin foco. Seishoras después comienza con dolor intenso a nivelhipogástrico y resistencia abdominal. La analítica escompatible con una sepsis grave con coagulopatia.

  4. Aetiology of neonatal sepsis in Blantyre, Malawi: 1996-2001

    NARCIS (Netherlands)

    Milledge, J.; Calis, J. C. J.; Graham, S. M.; Phiri, A.; Wilson, L. K.; Soko, D.; Mbvwinji, M.; Walsh, A. L.; Rogerson, S. R.; Molyneux, M. E.; Molyneux, E. M.

    2005-01-01

    The aim of this retrospective study was to report causes, antibiotic resistance and outcome of neonatal sepsis (often fatal in developing countries) in Malawi. All blood and cerebrospinal fluid isolates collected between January 1996 and December 2001 from inpatients aged 0-30 days with suspected

  5. Prevention of wound sepsis in amputations by peri-operative ...

    African Journals Online (AJOL)

    cellulitis. + cellulitis Toes foot Leg. 15. 1. 15. 6. 19. 6. 7. 1. 5. 8. 5. - -. 22. 2. 20. 6. 27. 11. Total. Group. A-CA combination of amoxycillin and clavulanic acid (A-CA) (Aug- mentin; Beecham), was studied and its efficacy in preventing amputation wound sepsis determined. In this combination the amoxycillin is supplemented by ...

  6. Listeria monocytogenes infection in pregnancy and neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Francesca Pascale

    2008-06-01

    Full Text Available Authors report a fatal neonatal sepsis caused by Listeria monocytogenes. While the diagnostic procedure aimed to identify the microrganism is described, it is emphasized the importance to recover Streptococcus agalactiae (GBS and L. monocytogenes by means of vaginal-rectal swab culture. The intrapartum screening for L. monocytogenes, by Polymerase Chain Reaction (PCR providing results in 75 minutes is also evaluated.

  7. Secretory phospholipase A(2) in newborn infants with sepsis

    NARCIS (Netherlands)

    Schrama, A. J. J.; De Beaufort, A. J.; Poorthuis, B. J. H. M.; Berger, H. M.; Walther, F. J.

    2008-01-01

    Objective: To investigate secretory phospholipase A(2) ( sPLA(2)) activity in neonatal sepsis. Study Design: Plasma sPLA(2) activity, C- reactive protein ( CRP) concentration, leukocyte count and immature/ total neutrophil ( I/ T) ratio were assessed in a group of 156 infants admitted for neonatal

  8. Diagnostic value of procalcitonin in neonatal sepsis | Arowosegbe ...

    African Journals Online (AJOL)

    Introduction: Neonatal sepsis is a major cause of mortality in developing countries. Accurate and quick diagnosis are difficult because clinical presentation are non-specific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. Serum procalcitonin (PCT) has been proposed as an ...

  9. Stable rates of neonatal sepsis in a tertiary neonatal unit.

    Science.gov (United States)

    Lean, Wei Ling; Kamlin, Camille O; Garland, Suzanne M; Jacobs, Susan E

    2015-03-01

    To describe the rate of early- and late-onset sepsis in neonates admitted to the neonatal intensive care unit at the Royal Women's Hospital and to compare the rate of late-onset sepsis (LOS) with a published (2008) cohort from the same unit. The secondary aim was to examine clinicians' compliance with antibiotic guidelines. Infants born sepsis and compliance with antibiotic guidelines were applied. One hundred and seventy-two infants met the inclusion criteria, with 152 having blood culture evaluations for early-onset sepsis (EOS) and 58 having 109 evaluations for LOS. Definite EOS occurred in 1.3% with Escherichia coli isolated. The rate of definite LOS in 2011 of 22% was not significantly different than the 27% in 2008, with coagulase-negative staphylococcus the main isolate. Antibiotic continuation beyond 72 h in infants with negative blood cultures was the main reason for non-compliance with antibiotic guidelines. The rate of EOS is comparable with published reports and the rate of LOS has remained stable over a 3-year period. Discontinuation of antibiotics with negative septic markers and blood cultures at 48-72 h is encouraged. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  10. Time for a neonatal–specific consensus definition for sepsis

    Science.gov (United States)

    Wynn, James L.; Wong, Hector R.; Shanley, Thomas P.; Bizzarro, Matthew J.; Saiman, Lisa; Polin, Richard A.

    2014-01-01

    Objective To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. Study selection The review focused primarily on pediatric literature relevant to the topic of interest. Conclusions Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates. PMID:24751791

  11. [Mycotic coronary aneurysm with Escherichia coli sepsis: a case report].

    Science.gov (United States)

    Lemoine, J; Popovic, B; Amrein, D; Lemoine, S; Angioi, M; Moulin, F; Ethevenot, G; Aliot, E; Brembilla Perrot, B

    2007-06-01

    We report the case of a patient who was admitted for acute coronary syndrom associated with fever originating from urinary tract. Coronary arteriography revealed a huge coronary aneurysm which ruptured a short time after diagnosis. After surgery, it was proven to be mycotic aneurysm related to Escherichia Coli sepsis.

  12. Profile of Neonatal Sepsis due to Burkholderia capacia Complex.

    Science.gov (United States)

    Chandrasekaran, Aparna; Subburaju, Nivedhana; Mustafa, Muzamil; Putlibai, Sulochana

    2016-12-15

    We report the result of retrospective record review of the clinical profile of 59 neonates who presented to a tertiary-care extramural neonatal unit with Burkholderia cepacia complex infection. Among the 3265 admissions over 45 months, incidence of Burkholderia sepsis was 18 per 1000 admissions. Case fatality rate was 17%. Most (95%) isolates were sensitive to cotrimoxazole.

  13. A Report on Antibiotic Management of Neonatal Sepsis Caused by ...

    African Journals Online (AJOL)

    After respiratory failure detection, the baby was intubated and placed on mechanical ventilation for respiratory failure and was shifted to NICU. Ampicillin and gentamicin were instituted empirically. Enterobacter spp-induced severe sepsis was diagnosed. Included in the antibiotic therapy were oxacycline, amikacin, cefepime ...

  14. Risk factors and antibiogram of organisms causing puerperal sepsis ...

    African Journals Online (AJOL)

    Background: Puerperal sepsis is a common pregnancy related complication and is one of the leading causes of maternal morbidity and mortality in Sub Saharan Africa. There is paucity of regional data on the antibiogram and risk factors associated with this condition, Aim: To determine the risk factors, aetiological organisms ...

  15. Procalcitonin: a reliable marker for the diagnosis of neonatal sepsis.

    Science.gov (United States)

    Adib, Minoo; Bakhshiani, Zahra; Navaei, Fakhri; Saheb Fosoul, Fereshteh; Fouladi, Salomeh; Kazemzadeh, Hamidreza

    2012-03-01

    In the last few years, serum procalcitonin has been proposed as an early marker of infections in neonates, with varying results. In this study, we aimed to investigate the value of procalcitonin, and C- reactive protein in establishing the diagnosis of neonatal sepsis. Blood samples were collected at admission from 69 neonates with suspected infection (admitted to the Neonatal Intensive Care Units at Alzahra and Dr Beheshti Hospital in and Fatema-Zahra in Najafabad from May 2005 to April 2006). Patients were categorized in different groups according to clinical symptoms of sepsis, bacteriological and laboratory results. Group I consisted of 20 newborns with positive blood cultures and other biological tests which suggested infection. Group II consisted of 49 neonates with negative blood cultures but had two or three of clinical signs of sepsis. The control group included 18 healthy neonates with physiological hyperbilirubinemia and no clinical and biological data of infection, referred to the hospital for bilirubin determination. Procalcitonin and C-reactive protein (CRP) were determined by immunoluminometric assay and nephlometry method respectively. Mean levels of procalcitonin and CRP in septic neonates (group I) were significantly higher than the other two groups (P< 0.005). Sensitivity, specificity, positive predictive value and negative predictive value were determined for all markers and compared with each other. We conclude that procalcitonin is a better marker than CRP in the diagnosis of neonatal sepsis.

  16. Cytokines and anticytokines in the pathogenesis of sepsis

    NARCIS (Netherlands)

    van der Poll, T.; van Deventer, S. J.

    1999-01-01

    Clinical trials with anti-inflammatory agents in patients with sepsis are based on the assumption that excessive proinflammatory activity of the cytokine network negatively influences the outcome of severe bacterial infections. The failure of these trials to show clinical benefit, in conjunction

  17. Sepsis as 2 problems: Identifying sepsis at admission and predicting onset in the hospital using an electronic medical record-based acuity score.

    Science.gov (United States)

    Rothman, Michael; Levy, Mitchell; Dellinger, R Philip; Jones, Stephen L; Fogerty, Robert L; Voelker, Kirk G; Gross, Barry; Marchetti, Albert; Beals, Joseph

    2017-04-01

    Early identification and treatment improve outcomes for patients with sepsis. Current screening tools are limited. We present a new approach, recognizing that sepsis patients comprise 2 distinct and unequal populations: patients with sepsis present on admission (85%) and patients who develop sepsis in the hospital (15%) with mortality rates of 12% and 35%, respectively. Models are developed and tested based on 258 836 adult inpatient records from 4 hospitals. A "present on admission" model identifies patients admitted to a hospital with sepsis, and a "not present on admission" model predicts postadmission onset. Inputs include common clinical measurements and the Rothman Index. Sepsis was determined using International Classification of Diseases, Ninth Revision, codes. For sepsis present on admission, area under the curves ranged from 0.87 to 0.91. Operating points chosen to yield 75% and 50% sensitivity achieve positive predictive values of 17% to 25% and 29% to 40%, respectively. For sepsis not present on admission, at 65% sensitivity, positive predictive values ranged from 10% to 20% across hospitals. This approach yields good to excellent discriminatory performance among adult inpatients for predicting sepsis present on admission or developed within the hospital and may aid in the timely delivery of care. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis [corrected].

    Directory of Open Access Journals (Sweden)

    Weera Mahavanakul

    Full Text Available The Surviving Sepsis Campaign (SSC guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting.We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53% of who died within 28 days. One third of patients were treated in intensive care units (ICUs. Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis.It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries.

  19. 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

    2011-04-01

    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. © Tohoku University Medical Press

  20. Extracellular administration of BCL2 protein reduces apoptosis and improves survival in a murine model of sepsis.

    Directory of Open Access Journals (Sweden)

    Akiko Iwata

    2011-02-01

    Full Text Available Severe sepsis and septic shock are major causes of morbidity and mortality worldwide. In experimental sepsis there is prominent apoptosis of various cell types, and genetic manipulation of death and survival pathways has been shown to modulate organ injury and survival.We investigated the effect of extracellular administration of two anti-apoptotic members of the BCL2 (B-cell lymphoma 2 family of intracellular regulators of cell death in a murine model of sepsis induced by cecal ligation and puncture (CLP. We show that intraperitoneal injection of picomole range doses of recombinant human (rh BCL2 or rhBCL2A1 protein markedly improved survival as assessed by surrogate markers of death. Treatment with rhBCL2 or rhBCL2A1 protein significantly reduced the number of apoptotic cells in the intestine and heart following CLP, and this was accompanied by increased expression of endogenous mouse BCL2 protein. Further, mice treated with rhBCL2A1 protein showed an increase in the total number of neutrophils in the peritoneum following CLP with reduced neutrophil apoptosis. Finally, although neither BCL2 nor BCL2A1 are a direct TLR2 ligand, TLR2-null mice were not protected by rhBCL2A1 protein, indicating that TLR2 signaling was required for the protective activity of extracellularly adminsitered BCL2A1 protein in vivo.Treatment with rhBCL2A1 or rhBCL2 protein protects mice from sepsis by reducing apoptosis in multiple target tissues, demonstrating an unexpected, potent activity of extracellularly administered BCL2 BH4-domain proteins.

  1. Hyperglycemia and glycemic variability are associated with the severity of sepsis in nondiabetic subjects.

    Science.gov (United States)

    Preechasuk, Lukana; Suwansaksri, Nattakarn; Ipichart, Nantawan; Vannasaeng, Sathit; Permpikul, Chairat; Sriwijitkamol, Apiradee

    2017-04-01

    The purpose was to compare glucose variability (GV) obtained via continuous glucose monitoring between nondiabetic sepsis patients and healthy subjects and to seek associations between GV and sepsis severity in nondiabetic sepsis patients. Nondiabetic sepsis inpatients and healthy controls received a 72-hour continuous glucose monitoring (iPro2, Medtronic) postadmission and post-oral glucose tolerance test, respectively. The mean glucose level (MGL) along with GV represented by standard deviation (SD) and the mean amplitude of glycemic excursion (MAGE) were calculated at 24 and 72 hours. Sepsis severity was evaluated with the Sepsis-related Organ Failure Assessment Score (SOFA). MGL and GV in patients with SOFA ≥9 and sepsis and 10 healthy subjects were recruited. No differences were found between groups except for higher patient age in sepsis patients. The MGL and MAGE 72h of sepsis patients were significantly higher than those of healthy subjects. MGL and GV 24h were higher in patients with SOFA ≥9 than in patients with SOFA sepsis patients had higher MGL and GV values than healthy subjects. MGL and GV 24h were associated with sepsis severity. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Reactivation of multiple viruses in patients with sepsis.

    Directory of Open Access Journals (Sweden)

    Andrew H Walton

    Full Text Available A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV, Epstein-Barr (EBV, herpes-simplex (HSV, human herpes virus-6 (HHV-6, and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%, EBV (53.2%, HSV (14.1%, HHV-6 (10.4%, and TTV (77.5%. 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5-8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104-106 DNA copies/ml blood for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p<0.05. Reactivation of latent viruses is common with prolonged sepsis, with frequencies similar to

  3. The recognition and management of sepsis and septic shock: a guide for non-intensivists.

    Science.gov (United States)

    Keeley, Alexander; Hine, Paul; Nsutebu, Emmanuel

    2017-10-01

    Sepsis is common, often fatal and requires rapid interventions to improve outcomes. While the optimal management of sepsis in the intensive care setting is the focus of extensive research interest, the mainstay of the recognition and initial management of sepsis will occur outside the intensive care setting. Therefore, it is key that institutions and clinicians remain well informed of the current updates in sepsis management and continue to use them to deliver appropriate and timely interventions to enhance patient survival. This review discusses the latest updates in sepsis care including the new consensus definition of sepsis, the outcome of the proCESS, ProMISe and ARISE trials of early goal directed therapy (EGDT), and the most recent guidelines from the Surviving Sepsis Campaign. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Therapeutic effects of compound hypertonic saline on rats with sepsis

    Directory of Open Access Journals (Sweden)

    Fang Dong

    2014-09-01

    Full Text Available Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

  5. Descriptive analysis of sepsis in a developing country.

    Science.gov (United States)

    Dagher, Gilbert Abou; Saadeldine, Mothana; Bachir, Rana; Zebian, Dina; Chebl, Ralphe Bou

    2015-01-01

    Most studies on sepsis were conducted in developed countries. The aim of this study is to report on a series of patients with sepsis in a tertiary hospital in a developing country. Patients admitted through the emergency department of a single university-based institution between January 2008 and June 2012, with a final diagnosis of sepsis, bacteremia, or septic shock, were retrieved. A sample of 97 patients was selected. Vital signs at presentation, number of SIRS criteria, use of vasopressors and steroids, and in-hospital mortality were recorded. The mean age was 70.09 ± 16.82, ranging from 19 to 96 years; 48.5 % were females and 51.5 % were males; 42.3 % of the patients were found to be bacteremic. IV fluid requirement during the first 6 h was 1.75 ± 1.96 l. The time for antibiotic initiation was 3.43 ± 4.48 h, with 87.6 % of the antibiotics initiated in the emergency department. Norepinephrine was the most commonly used vasopressor (38.1 %) followed by dopamine (8.2 %), and the inotrope dobutamine (4.1 %); 45.3 % of the patients were admitted to the intensive care unit (ICU), and the remaining 54.7 % were managed on the general practice unit (GPU). A total of 30 (30.9 %) septic patients died. The 28-day mortality was 20.6 %. Deceased patients had greater vasopressor use, a longer stay in the ICU (p = 0.001), and a longer time to norepinephrine use (p = 0.004). This is the first study providing an in-depth analysis of sepsis patients in a developing country, looking at in-hospital mortality, SIRS criteria utility, and at the overall sepsis management.

  6. Sinomenine Hydrochloride Protects against Polymicrobial Sepsis via Autophagy

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    Yu Jiang

    2015-01-01

    Full Text Available Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs. The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl is widely used to treat rheumatoid arthritis (RA. However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3 puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM. 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.

  7. Therapeutic effects of compound hypertonic saline on rats with sepsis.

    Science.gov (United States)

    Dong, Fang; Chen, Wei; Xu, Liang; Wang, Huabing; Lu, Huizhi

    2014-01-01

    Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  8. Therapeutic effects of compound hypertonic saline on rats with sepsis

    Directory of Open Access Journals (Sweden)

    Fang Dong

    Full Text Available Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

  9. Culture-positive sepsis in neonatal camelids: 21 cases.

    Science.gov (United States)

    Dolente, Brett A; Lindborg, Susan; Palmer, Jonathan E; Wilkins, Pamela A

    2007-01-01

    There is limited literature on neonatal bacterial sepsis in New World (NW) camelids. Bacterial culture-positive crias have clinical differences based on the specific bacterial genera isolated. Bacterial culture-positive NW camelid crias <21 days of age from 1990 to 2005 were included. Historic physical examination and cliniopathologic data were retrieved from medical records as were the identity and antibiograms of bacterial isolates. Cases were categorized by outcome (survival versus nonsurvival) and type of sepsis (gram-negative or gram-positive). Kruskal-Wallis and chi-square testing were used to evaluate differences between groups. Twenty-one crias met the inclusion criteria. Median age was 2 days. Failure of passive transfer was common. There were few differences identified on the basis of outcome or type of sepsis. Crias without gastrointestinal or central nervous system involvement survived in greater numbers. Forty-six percent of isolates were gram-positive. The most common isolates were the following: Escherichia coli, Enterococcus spp., Listeria monocytogenes, and Citrobacter spp. Overall survival was 67% (14/21). Crias with sepsis do not appear to present with major biochemical, hematologic, or blood gas abnormalities, potentially complicating diagnosis. Affected crias may not have localizing signs at presentation and are not usually febrile, although hypothermia, tachypnea, and tachycardia are relatively common. Total protein concentration was not a substitute for immunoglobulin G measurement in septic crias in this study. Familiarity with the clinical presentation and common pathogens isolated should improve early recognition and treatment and ultimately outcome of crias with sepsis.

  10. Sepsis risk factors in infants with congenital diaphragmatic hernia.

    Science.gov (United States)

    Levy, Michaël; Le Sache, Nolwenn; Mokhtari, Mostafa; Fagherazzi, Guy; Cuzon, Gaelle; Bueno, Benjamin; Fouquet, Virginie; Benachi, Alexandra; Eleni Dit Trolli, Sergio; Tissieres, Pierre

    2017-12-01

    Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly and remains among the most challenging ICU-managed disease. Beside severe pulmonary hypertension, lung hypoplasia and major abdominal surgery, infective complications remain major determinants of outcome. However, the specific incidence of sepsis as well as associated risk factors is unknown. This prospective, 4-year observational study took place in the pediatric intensive care and neonatal medicine department of the Paris South University Hospitals (Le Kremlin-Bicêtre, France), CDH national referral center and involved 62 neonates with CDH. During their ICU stay, 28 patients (45%) developed 38 sepsis episodes. Ventilator-associated pneumonia (VAP: 23/38; 31.9 VAP per 1000 days of mechanical ventilation) and central line-associated blood stream infections (CLABSI: 5/38; 5.5 per 1000 line days) were the most frequently encountered infections. Multivariate analysis showed that gestational age at birth and intra-thoracic position of liver were significantly associated with the occurrence of sepsis. Infected patients had longer duration of mechanical and noninvasive ventilation (16.2 and 5.8 days, respectively), longer delay to first feeding (1.2 days) and a longer length of stay in ICU (23 days), but there was no difference in mortality. Healthcare-associated infections, and more specifically VAP, are the main infective threat in children with CDH. Sepsis has a significant impact on the duration of ventilator support and ICU length of stay but does not impact mortality. Low gestational age and intra-thoracic localization of the liver are two independent risk factors associated with sepsis.

  11. Bayesian network analysis of multi-compartmentalized immune responses in a murine model of sepsis and direct lung injury.

    Science.gov (United States)

    Nemzek, Jean A; Hodges, Andrew P; He, Yongqun

    2015-09-30

    Inflammatory disease processes involve complex and interrelated systems of mediators. Determining the causal relationships among these mediators becomes more complicated when two, concurrent inflammatory conditions occur. In those cases, the outcome may also be dependent upon the timing, severity and compartmentalization of the insults. Unfortunately, standard methods of experimentation and analysis of data sets may investigate a single scenario without uncovering many potential associations among mediators. However, Bayesian network analysis is able to model linear, nonlinear, combinatorial, and stochastic relationships among variables to explore complex inflammatory disease systems. In these studies, we modeled the development of acute lung injury from an indirect insult (sepsis induced by cecal ligation and puncture) complicated by a direct lung insult (aspiration). To replicate multiple clinical situations, the aspiration injury was delivered at different severities and at different time intervals relative to the septic insult. For each scenario, we measured numerous inflammatory cell types and cytokines in samples from the local compartments (peritoneal and bronchoalveolar lavage fluids) and the systemic compartment (plasma). We then analyzed these data by Bayesian networks and standard methods. Standard data analysis demonstrated that the lung injury was actually reduced when two insults were involved as compared to one lung injury alone. Bayesian network analysis determined that both the severity of lung insult and presence of sepsis influenced neutrophil recruitment and the amount of injury to the lung. However, the levels of chemoattractant cytokines responsible for neutrophil recruitment were more strongly linked to the timing and severity of the lung insult compared to the presence of sepsis. This suggests that something other than sepsis-driven exacerbation of chemokine levels was influencing the lung injury, contrary to previous theories. To our

  12. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations.

    Science.gov (United States)

    Fleischmann, Carolin; Scherag, André; Adhikari, Neill K J; Hartog, Christiane S; Tsaganos, Thomas; Schlattmann, Peter; Angus, Derek C; Reinhart, Konrad

    2016-02-01

    Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale. To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies. We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years. The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215-386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98-226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334-571; τ = 0.38) for sepsis and 270 (95% CI, 176-412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually. Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.

  13. Formal Modelling of Toll like Receptor 4 and JAK/STAT Signalling Pathways: Insight into the Roles of SOCS-1, Interferon-β and Proinflammatory Cytokines in Sepsis

    Science.gov (United States)

    Paracha, Rehan Zafar; Ahmad, Jamil; Ali, Amjad; Hussain, Riaz; Niazi, Umar; Tareen, Samar Hayat Khan; Aslam, Babar

    2014-01-01

    Sepsis is one of the major causes of human morbidity and results in a considerable number of deaths each year. Lipopolysaccharide-induced sepsis has been associated with TLR4 signalling pathway which in collaboration with the JAK/STAT signalling regulate endotoxemia and inflammation. However, during sepsis our immune system cannot maintain a balance of cytokine levels and results in multiple organ damage and eventual death. Different opinions have been made in previous studies about the expression patterns and the role of proinflammatory cytokines in sepsis that attracted our attention towards qualitative properties of TLR4 and JAK/STAT signalling pathways using computer-aided studies. René Thomas’ formalism was used to model septic and non-septic dynamics of TLR4 and JAK/STAT signalling. Comparisons among dynamics were made by intervening or removing the specific interactions among entities. Among our predictions, recurrent induction of proinflammatory cytokines with subsequent downregulation was found as the basic characteristic of septic model. This characteristic was found in agreement with previous experimental studies, which implicate that inflammation is followed by immunomodulation in septic patients. Moreover, intervention in downregulation of proinflammatory cytokines by SOCS-1 was found desirable to boost the immune responses. On the other hand, interventions either in TLR4 or transcriptional elements such as NFκB and STAT were found effective in the downregulation of immune responses. Whereas, IFN-β and SOCS-1 mediated downregulation at different levels of signalling were found to be associated with variations in the levels of proinflammatory cytokines. However, these predictions need to be further validated using wet laboratory experimental studies to further explore the roles of inhibitors such as SOCS-1 and IFN-β, which may alter the levels of proinflammatory cytokines at different stages of sepsis. PMID:25255432

  14. Increased CD4(+) T cell co-inhibitory immune receptor CEACAM1 in neonatal sepsis and soluble-CEACAM1 in meningococcal sepsis: a role in sepsis-associated immune suppression?

    NARCIS (Netherlands)

    Flier, M. van der; Sharma, D.B.; Estevao, S.; Emonts, M.; Rook, D.; Hazelzet, J.A.; Goudoever, J.B. van; Hartwig, N.G.

    2013-01-01

    The co-inhibitory immune receptor carcinoembryonic antigen-related cell-adhesion molecule 1 (CEACAM1) and its self-ligand CEACAM1 can suppress T cell function. Suppression of T cell function in sepsis is well documented. Late-onset neonatal sepsis in VLBW-infants was associated with an increased

  15. Increased CD4+ T Cell Co-Inhibitory Immune Receptor CEACAM1 in Neonatal Sepsis and Soluble-CEACAM1 in Meningococcal Sepsis: A Role in Sepsis-Associated Immune Suppression?

    NARCIS (Netherlands)

    M. van der Flier (Michiel); D.B. Sharma (Dyana); S. Estevão (Silvia); M. Emonts (Marieke); D. Rook (Denise); J.A. Hazelzet (Jan); J.B. van Goudoever (Hans); N.G. Hartwig (Nico)

    2013-01-01

    textabstractThe co-inhibitory immune receptor carcinoembryonic antigen-related cell-adhesion molecule 1 (CEACAM1) and its self-ligand CEACAM1 can suppress T cell function. Suppression of T cell function in sepsis is well documented. Late-onset neonatal sepsis in VLBW-infants was associated with an

  16. Sepsis National Hospital Inpatient Quality Measure (SEP-1): Multistakeholder Work Group Recommendations for Appropriate Antibiotics for the Treatment of Sepsis.

    Science.gov (United States)

    Septimus, Edward J; Coopersmith, Craig M; Whittle, Jessica; Hale, Caleb P; Fishman, Neil O; Kim, Thomas J

    2017-10-16

    The Center for Medicare and Medicaid Services adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting Program in July 2015 to help address the high mortality and high cost associated with sepsis. The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multistakeholder workgroup recognizes the need for SEP-1 but strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, is not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the workgroup provides recommendations for appropriate antibiotics for the treatment of sepsis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  17. C-Reactive Protein and Hemogram Parameters for the Non-Sepsis Systemic Inflammatory Response Syndrome and Sepsis: What Do They Mean?

    Science.gov (United States)

    Gucyetmez, Bulent; Atalan, Hakan K

    2016-01-01

    Sepsis is one of the most common reasons of increased mortality and morbidity in the intensive care unit. The changes in CRP levels and hemogram parameters and their combinations may help to distinguish sepsis from non-sepsis SIRS. The aim of this study is to investigate the CRP and hemogram parameters as an indicator of sepsis. A total of 2777 patients admitted to the ICU of two centers between 2006-2013 were evaluated retrospectively. The patients were diagnosed as SIRS (-), non-sepsis SIRS and sepsis. The patients who were under 18 years old, re-admitted, diagnosed with hematological disease, on corticosteroid and immunosuppressive therapy, SIRS (-), culture negative, undocumented laboratory values and outcomes were excluded. 1257 patients were divided into 2 groups as non-sepsis SIRS and sepsis. The patients' demographic data, CRP levels, hemogram parameters, length of ICU stay and mortality were recorded. 1257 patients were categorized as non-sepsis SIRS (816, 64.9%) and sepsis (441, 35.1%). In the multivariate analysis, the likelihood of sepsis was increased 3.2 (2.2-4.6), 1.7 (1.2-2.4), 1.6 (1.2-2.1), 2.3 (1.4-3.8), 1.5 (1.1-2.1) times by the APACHE II≥13, SOFA score≥4, CRP≥4.0, LymC<0.45 and PLTC<150 respectively (p<0.001 p = 0.007 p = 0.004 p<0.001 p = 0.027). The likelihood of sepsis was increased 18.1 (8.4-38.7) times by the combination of CRP≥4.0, lymC<0.45 and PLTC<150 (P<0.001). While WBCC, NeuC, Neu%, NLCR and EoC are far from being the indicators to distinguish sepsis from non-sepsis SIRS, the combinations of CRP, LymC and PLTC can be used to determine the likelihood of sepsis.

  18. C-Reactive Protein and Hemogram Parameters for the Non-Sepsis Systemic Inflammatory Response Syndrome and Sepsis: What Do They Mean?

    Directory of Open Access Journals (Sweden)

    Bulent Gucyetmez

    Full Text Available Sepsis is one of the most common reasons of increased mortality and morbidity in the intensive care unit. The changes in CRP levels and hemogram parameters and their combinations may help to distinguish sepsis from non-sepsis SIRS. The aim of this study is to investigate the CRP and hemogram parameters as an indicator of sepsis.A total of 2777 patients admitted to the ICU of two centers between 2006-2013 were evaluated retrospectively. The patients were diagnosed as SIRS (-, non-sepsis SIRS and sepsis. The patients who were under 18 years old, re-admitted, diagnosed with hematological disease, on corticosteroid and immunosuppressive therapy, SIRS (-, culture negative, undocumented laboratory values and outcomes were excluded. 1257 patients were divided into 2 groups as non-sepsis SIRS and sepsis. The patients' demographic data, CRP levels, hemogram parameters, length of ICU stay and mortality were recorded.1257 patients were categorized as non-sepsis SIRS (816, 64.9% and sepsis (441, 35.1%. In the multivariate analysis, the likelihood of sepsis was increased 3.2 (2.2-4.6, 1.7 (1.2-2.4, 1.6 (1.2-2.1, 2.3 (1.4-3.8, 1.5 (1.1-2.1 times by the APACHE II≥13, SOFA score≥4, CRP≥4.0, LymC<0.45 and PLTC<150 respectively (p<0.001 p = 0.007 p = 0.004 p<0.001 p = 0.027. The likelihood of sepsis was increased 18.1 (8.4-38.7 times by the combination of CRP≥4.0, lymC<0.45 and PLTC<150 (P<0.001.While WBCC, NeuC, Neu%, NLCR and EoC are far from being the indicators to distinguish sepsis from non-sepsis SIRS, the combinations of CRP, LymC and PLTC can be used to determine the likelihood of sepsis.

  19. Culture proven newborn sepsis with a special emphasis on late onset sepsis caused by Enterobacteriaceae in a level III neonatal care unit in Astana, Kazakhstan.

    Science.gov (United States)

    Kangozhinova, Kalamkas; Abentayeva, Botakoz; Repa, Andreas; Baltabayeva, Assem; Erwa, Wolfgang; Stauffer, Friedrich

    2013-10-01

    Newborn sepsis is one of the major public health concerns worldwide. Also in our neonatal care unit, it is one of the major problems and especially infections with Enterobacteriaceae were noted to pose an increasing problem in the last years. Data collection was done retrospectively for 2011. Early onset sepsis was defined as having a positive blood culture within 72 h and late onset sepsis after 72 h of delivery. Out of 599 patients being admitted, 58 newborns were assessed having a neonatal sepsis. Of these 58 newborns with sepsis, 11 were diagnosed within 72 h post delivery (early onset) and 47 were diagnosed after 72 h post delivery (late onset). The percentage of Enterobacteriaceae causing late onset sepsis was 57.5 %. Among these, Klebsiella pneumoniae could be isolated in 29.8 %, Enterobacter cloacae in 12.8 %, Enterobacter aerogenes in 8.5 %, and Escherichia coli in 6.4 % of late onset sepsis. Majority of the strains showed a resistance to antibiotics used in empiric treatment. Antibiotic prophylaxis/treatment from birth until the onset of late onset sepsis could be analyzed in 20 out of 27 newborns with late onset sepsis caused by Enterobacteriaceae. A regimen of empirical antibiotic treatment containing aminopenicillin and/or gentamicin was administered in 16 newborns and that of cephalosporin in 14 out of 20 newborns for at least 5 days before onset of sepsis. The association of empiric long-term antibiotic treatment and the high number of late onset sepsis with often multiresistant Enterobacteriaceae might be causal and urges for a change in general antibiotic prophylaxis/treatment in newborns admitted to the neonatal care unit of our hospital.

  20. New Sepsis Definition (Sepsis-3) and Community-acquired Pneumonia Mortality. A Validation and Clinical Decision-Making Study.

    Science.gov (United States)

    Ranzani, Otavio T; Prina, Elena; Menéndez, Rosario; Ceccato, Adrian; Cilloniz, Catia; Méndez, Raul; Gabarrus, Albert; Barbeta, Enric; Bassi, Gianluigi Li; Ferrer, Miquel; Torres, Antoni

    2017-11-15

    The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia. This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality. Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality. qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.