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Sample records for experimental hyperdynamic sepsis

  1. Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

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    Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

    2012-08-01

    Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

  2. The impact of intrarenal nitric oxide synthase inhibition on renal blood flow and function in mild and severe hyperdynamic sepsis.

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    Ishikawa, Ken; Bellomo, Rinaldo; May, Clive N

    2011-04-01

    In experimental hyperdynamic sepsis, renal function deteriorates despite renal vasodilatation and increased renal blood flow. Because nitric oxide is increased in sepsis and participates in renal blood flow control, we investigated the effects of intrarenal Nω-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis. Prospective crossover and randomized control interventional studies. University-affiliated research institute. Thirty-two merino ewes. Examination of responses to intrarenal infusion of Nω-nitro-L-arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and in sheep administered Escherichia coli. : In normal sheep, Nω-nitro-L-arginine methyl ester decreased renal blood flow (301 ± 30 to 228 ± 26 mL/min) and creatinine clearance (40.0 ± 5.8 to 31.1 ± 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma creatinine increased and there were decreases in creatinine clearance (34.5 ± 4.6 to 20.1 ± 3.7 mL/min) and fractional excretion of sodium despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester normalized renal blood flow and increased urine output, but creatinine clearance did not improve and plasma creatinine and fractional excretion of sodium increased. In sheep with severe hypotensive sepsis, creatinine clearance decreased further (31.1 ± 5.4 to 16.0 ± 1.7 mL/min) despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester restored mean arterial pressure and reduced renal blood flow but did not improve plasma creatinine or creatinine clearance. In hyperdynamic sepsis, with or without hypotension, creatinine clearance decreased despite increasing renal blood flow. Intrarenal Nω-nitro-L-arginine methyl ester infusion reduced renal blood flow but did not improve creatinine clearance. These data indicate that septic acute kidney

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

    International Nuclear Information System (INIS)

    Bersten, A.D.; Gnidec, A.A.; Rutledge, F.S.; Sibbald, W.J.

    1990-01-01

    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

  4. Experimental sepsis impairs humoral memory in mice.

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    Christian Pötschke

    Full Text Available Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool's development, which is not complete 8 weeks after secondary immunization.

  5. 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...

  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. Sepsis

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    ... mild sepsis, but the mortality rate for septic shock is nearly 50 percent. Also, an episode of severe sepsis may ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  8. Sepsis

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

    2016-01-01

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

  9. Sepsis

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    Perner, Anders; Rhodes, Andrew; Venkatesh, Bala

    2017-01-01

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

  10. Dexmedetomidine attenuates the microcirculatory derangements evoked by experimental sepsis.

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    Miranda, Marcos L; Balarini, Michelle M; Bouskela, Eliete

    2015-03-01

    Dexmedetomidine, an α-2 adrenergic receptor agonist, has already been used in septic patients although few studies have examined its effects on microcirculatory dysfunction, which may play an important role in perpetuating sepsis syndrome. Therefore, the authors have designed a controlled experimental study to characterize the microcirculatory effects of dexmedetomidine in an endotoxemia rodent model that allows in vivo studies of microcirculation. After skinfold chamber implantation, 49 golden Syrian hamsters were randomly allocated in five groups: (1) control animals; (2) nonendotoxemic animals treated with saline; (3) nonendotoxemic animals treated with dexmedetomidine (5.0 μg kg h); (4) endotoxemic (lipopolysaccharide 1.0 mg/kg) animals treated with saline; and (5) endotoxemic animals treated with dexmedetomidine. Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Mean arterial blood pressure, heart rate, arterial blood gases, and lactate concentrations were also documented. Lipopolysaccharide administration increased leukocyte rolling and adhesion and decreased capillary perfusion. Dexmedetomidine significantly attenuated these responses: compared with endotoxemic animals treated with saline, those treated with dexmedetomidine had less leukocyte rolling (11.8 ± 7.2% vs. 24.3 ± 15.0%; P the end of the experiment. Dexmedetomidine decreased lipopolysaccharide-induced leukocyte-endothelial interactions in the hamster skinfold chamber microcirculation. This was accompanied by a significant attenuation of capillary perfusion deficits, suggesting that dexmedetomidine yields beneficial effects on endotoxemic animals' microcirculation.

  11. 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...... of spontaneous porcine pyemia including endocarditis and associated brain lesions. We present a porcine model of haematogenous S. aureus induced brain infection. Materials and Methods: Twelve pigs received an intravenous injection of S. aureus of 108 CFU/kg body weight once at 0h or twice at 0h and 12h. Four...... 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...

  12. Increased NTPDase Activity in Lymphocytes during Experimental Sepsis

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    Bertoncheli, Claudia de Mello; Zimmermann, Carine Eloise Prestes; Jaques, Jeandre Augusto dos Santos; Leal, Cláudio Alberto Martins; Ruchel, Jader Betsch; Rocha, Bruna Cipolatto; Pinheiro, Kelly de Vargas; Souza, Viviane do Carmo Gonçalves; Stainki, Daniel Roulim; Luz, Sônia Cristina Almeida; Schetinger, Maria Rosa Chitolina; Leal, Daniela Bitencourt Rosa

    2012-01-01

    We investigated in rats induced to sepsis the activity of ectonucleoside triphosphate diphosphohydrolase (NTPDase; CD39; E.C. 3.6.1.5), an enzyme involved in the modulation of immune responses. After 12 hours of surgery, lymphocytes were isolated from blood and NTPDase activity was determined. It was also performed the histology of kidney, liver, and lung. The results demonstrated an increase in the hydrolysis of adenosine-5′-triphosphate (ATP) (P 0.05). Histological analysis showed several morphological changes in the septic group, such as vascular congestion, necrosis, and infiltration of mononuclear cells. It is known that the intracellular milieu contains much more ATP nucleotides than the extracellular. In this context, the increased ATPasic activity was probably induced as a dynamic response to clean up the elevated ATP levels resulting from cellular death. PMID:22645477

  13. 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.

  14. 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.

  15. 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.

  16. Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis

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    Renko, Marjo; Valkonen, Päivi; Tapiainen, Terhi; Kontiokari, Tero; Mattila, Pauli; Knuuttila, Matti; Svanberg, Martti; Leinonen, Maija; Karttunen, Riitta; Uhari, Matti

    2008-01-01

    Background Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. Results We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis. PMID:18334022

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

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming

    2018-01-01

    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.......Patients with cirrhosis and portal hypertension often develop complications from a variety of organ systems leading to a multiple organ failure. The combination of liver failure and portal hypertension result in a hyperdynamic circulatory state partly owing to simultaneous splanchnic and peripheral...... arterial vasodilatation. Increases in circulatory vasodilators are believed to be due to portosystemic shunting and bacterial translocation leading to redistribution of the blood volume with central hypovolemia. Portal hypertension per se and increased splanchnic blood flow are mainly responsible...

  18. Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis.

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    Cuccurullo, Alessandra; Greco, Elisabetta; Lupia, Enrico; De Giuli, Paolo; Bosco, Ornella; Martin-Conte, Erica; Spatola, Tiziana; Turco, Emilia; Montrucchio, Giuseppe

    2016-01-01

    Thrombopoietin (TPO), a growth factor primarily involved in thrombopoiesis may also have a role in the pathophysiology of sepsis. In patients with sepsis, indeed, TPO levels are markedly increased, with disease severity being the major independent determinant of TPO concentrations. Moreover, TPO increases and correlates with ex vivo indices of platelet activation in patients with burn injury upon sepsis development, and may contribute to depress cardiac contractility in septic shock. Still, the role of TPO in sepsis pathophysiology remains controversial, given the protective role of TPO in other experimental disease models, for instance in doxorubicin-induced cardiotoxicity and myocardial ischemia/reperfusion injury. The aim of our study was to define the contribution of TPO in the development of organ damage induced by endotoxemia or sepsis, and to investigate the effects of inhibiting TPO in these conditions. We synthesized a chimeric protein able to inhibit TPO, mTPOR-MBP, and studied its effect in two murine experimental models, acute endotoxemia and cecal ligation and puncture (CLP) model. In both models, TPO levels markedly increased, from 289.80±27.87 pg/mL to 465.60±45.92 pg/mL at 3 hours in the LPS model (P<0.01), and from 265.00±26.02 pg/mL to 373.70±26.20 pg/mL in the CLP model (P<0.05), respectively. Paralleling TPO levels, also platelet-monocyte aggregates increased, from 32.86±2.48% to 46.13±1.39% at 3 hours in the LPS model (P<0.01), and from 43.68±1.69% to 56.52±4.66% in the CLP model (P<0.05). Blockade of TPO by mTPOR-MBP administration reduced histological damage in target organs, namely lung, liver, and gut. In particular, neutrophil infiltration and lung septal thickening were reduced from a score of 1.86±0.34 to 0.60±0.27 (P<0.01) and from 1.43±0.37 to 0.40±0.16 (P<0.05), respectively, in the LPS model at 3 hours, and from a score of 1.75±0.37 to 0.38±0.18 (P<0.01) and from 1.25±0.31 to 0.13±0.13 (P<0.001), respectively, in the

  19. Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis.

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    Alessandra Cuccurullo

    Full Text Available Thrombopoietin (TPO, a growth factor primarily involved in thrombopoiesis may also have a role in the pathophysiology of sepsis. In patients with sepsis, indeed, TPO levels are markedly increased, with disease severity being the major independent determinant of TPO concentrations. Moreover, TPO increases and correlates with ex vivo indices of platelet activation in patients with burn injury upon sepsis development, and may contribute to depress cardiac contractility in septic shock. Still, the role of TPO in sepsis pathophysiology remains controversial, given the protective role of TPO in other experimental disease models, for instance in doxorubicin-induced cardiotoxicity and myocardial ischemia/reperfusion injury. The aim of our study was to define the contribution of TPO in the development of organ damage induced by endotoxemia or sepsis, and to investigate the effects of inhibiting TPO in these conditions.We synthesized a chimeric protein able to inhibit TPO, mTPOR-MBP, and studied its effect in two murine experimental models, acute endotoxemia and cecal ligation and puncture (CLP model.In both models, TPO levels markedly increased, from 289.80±27.87 pg/mL to 465.60±45.92 pg/mL at 3 hours in the LPS model (P<0.01, and from 265.00±26.02 pg/mL to 373.70±26.20 pg/mL in the CLP model (P<0.05, respectively. Paralleling TPO levels, also platelet-monocyte aggregates increased, from 32.86±2.48% to 46.13±1.39% at 3 hours in the LPS model (P<0.01, and from 43.68±1.69% to 56.52±4.66% in the CLP model (P<0.05. Blockade of TPO by mTPOR-MBP administration reduced histological damage in target organs, namely lung, liver, and gut. In particular, neutrophil infiltration and lung septal thickening were reduced from a score of 1.86±0.34 to 0.60±0.27 (P<0.01 and from 1.43±0.37 to 0.40±0.16 (P<0.05, respectively, in the LPS model at 3 hours, and from a score of 1.75±0.37 to 0.38±0.18 (P<0.01 and from 1.25±0.31 to 0.13±0.13 (P<0.001, respectively

  20. 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.

  1. A novel animal model for hyperdynamic airway collapse.

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    Tsukada, Hisashi; O'Donnell, Carl R; Garland, Robert; Herth, Felix; Decamp, Malcolm; Ernst, Armin

    2010-12-01

    Tracheobronchomalacia (TBM) is increasingly recognized as a condition associated with significant pulmonary morbidity. However, treatment is invasive and complex, and because there is no appropriate animal model, novel diagnostic and treatment strategies are difficult to evaluate. We endeavored to develop a reliable airway model to simulate hyperdynamic airway collapse in humans. Seven 20-kg male sheep were enrolled in this study. Tracheomalacia was created by submucosal resection of > 50% of the circumference of 10 consecutive cervical tracheal cartilage rings through a midline cervical incision. A silicone stent was placed in the trachea to prevent airway collapse during recovery. Tracheal collapsibility was assessed at protocol-specific time points by bronchoscopy and multidetector CT imaging while temporarily removing the stent. Esophageal pressure and flow data were collected to assess flow limitation during spontaneous breathing. All animals tolerated the surgical procedure well and were stented without complications. One sheep died at 2 weeks because of respiratory failure related to stent migration. In all sheep, near-total forced inspiratory airway collapse was observed up to 3 months postprocedure. Esophageal manometry demonstrated flow limitation associated with large negative pleural pressure swings during rapid spontaneous inhalation. Hyperdynamic airway collapse can reliably be induced with this technique. It may serve as a model for evaluation of novel diagnostic and therapeutic strategies for TBM.

  2. Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells.

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    Yan, Jun; Mitra, Abhisek; Hu, Jiemiao; Cutrera, Jeffery J; Xia, Xueqing; Doetschman, Thomas; Gagea, Mihai; Mishra, Lopa; Li, Shulin

    2016-05-01

    Sepsis is an acute systemic inflammatory response to infection associated with high patient mortality (28-40%). We hypothesized that interleukin (IL)-30, a novel cytokine protecting mice against liver injury resulting from inflammation, would generate a protective effect against systemic inflammation and sepsis-induced death. Sepsis was induced by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). The inhibitory effects of IL-30 on septic inflammation and associated therapeutic effects were determined in wild-type, IL30 (p28)(-/-), IL10(-/-), and CD1d(-/-) mice. Mice treated with pIL30 gene therapy or recombinant IL-30 protein (rIL30) were protected from LPS-induced septic shock or CLP-induced polymicrobial sepsis and showed markedly less liver damage and lymphocyte apoptosis than control septic mice. The resulting reduction in mortality was mediated through attenuation of the systemic pro-inflammatory response and augmentation of bacterial clearance. Mice lacking IL-30 were more sensitive to LPS-induced sepsis. Natural killer-like T cells (NKT) produced much higher levels of IL-10 and lower levels of interferon-gamma and tumor necrosis factor-alpha in IL-30-treated septic mice than in control septic mice. Likewise, deficiency in IL-10 or NKT cells abolished the protective role of IL-30 against sepsis. Furthermore, IL-30 induced IL-10 production in purified and LPS-stimulated NKT cells. Blocking IL-6R or gp130 inhibited IL-30 mediated IL-10 production. IL-30 is important in modulating production of NKT cytokines and subsequent NKT cell-mediated immune regulation of other cells. Therefore, IL-30 has a role in prevention and treatment of sepsis via modulation of cytokine production by NKT. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. 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.

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

    International Nuclear Information System (INIS)

    Castro, C.L.; Aguiar-Nemer, A.S.; Castro-Faria-Neto, H.C.; Barros, F.R.; Rocha, E.M.S.; Silva-Fonseca, V.A.

    2013-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    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

  6. 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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    (-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...... (Ps...

  8. Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice.

    Science.gov (United States)

    Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D; Sarma, J Vidya; Zetoune, Firas S; Ward, Peter A

    2013-04-01

    Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Diffusion in periodic potentials with path integral hyperdynamics.

    Science.gov (United States)

    Ikonen, T; Khandkar, M D; Chen, L Y; Ying, S C; Ala-Nissila, T

    2011-08-01

    We consider the diffusion of brownian particles in one-dimensional periodic potentials as a test bench for the recently proposed stochastic path integral hyperdynamics (PIHD) scheme [Chen and Horing, J. Chem. Phys. 126, 224103 (2007)]. First, we consider the case where PIHD is used to enhance the transition rate of activated rare events. To this end, we study the diffusion of a single brownian particle moving in a spatially periodic potential in the high-friction limit at low temperature. We demonstrate that the boost factor as compared to straight molecular dynamics (MD) has nontrivial behavior as a function of the bias force. Instead of growing monotonically with the bias, the boost attains an optimal maximum value due to increased error in the finite path sampling induced by the bias. We also observe that the PIHD method can be sensitive to the choice of numerical integration algorithm. As the second case, we consider parallel resampling of multiple bias force values in the case of a brownian particle in a periodic potential subject to an external ac driving force. We confirm that there is no stochastic resonance in this system. However, while the PIHD method allows one to obtain data for multiple values of the ac bias, the boost with respect to MD remains modest due to the simplicity of the equation of motion in this case.

  10. Hyperdynamic left ventricular ejection fraction in the intensive care unit.

    Science.gov (United States)

    Paonessa, Joseph R; Brennan, Thomas; Pimentel, Marco; Steinhaus, Daniel; Feng, Mengling; Celi, Leo Anthony

    2015-08-07

    Limited information exists on the etiology, prevalence, and significance of hyperdynamic left ventricular ejection fraction (HDLVEF) in the intensive care unit (ICU). Our aim in the present study was to compare characteristics and outcomes of patients with HDLVEF with those of patients with normal left ventricular ejection fraction in the ICU using a large, public, deidentified critical care database. We conducted a longitudinal, single-center, retrospective cohort study of adult patients who underwent echocardiography during a medical or surgical ICU admission at the Beth Israel Deaconess Medical Center using the Multiparameter Intelligent Monitoring in Intensive Care II database. The final cohort had 2867 patients, of whom 324 had HDLVEF, defined as an ejection fraction >70%. Patients with an ejection fraction <55% were excluded. Compared with critically ill patients with normal left ventricular ejection fraction, the finding of HDLVEF in critically ill patients was associated with female sex, increased age, and the diagnoses of hypertension and cancer. Patients with HDLVEF had increased 28-day mortality compared with those with normal ejection fraction in multivariate logistic regression analysis adjusted for age, sex, Sequential Organ Failure Assessment score, Elixhauser score for comorbidities, vasopressor use, and mechanical ventilation use (odds ratio 1.38, 95% confidence interval 1.039-1.842, p =0.02). The presence of HDLVEF portended increased 28-day mortality, and may be helpful as a gravity marker for prognosis in patients admitted to the ICU. Further research is warranted to gain a better understanding of how these patients respond to common interventions in the ICU and to determine if pharmacologic modulation of HDLVEF improves outcomes.

  11. Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in locomotor and respiratory muscles during experimental sepsis in mice.

    Science.gov (United States)

    Morel, Jérome; Palao, Jean-Charles; Castells, Josiane; Desgeorges, Marine; Busso, Thierry; Molliex, Serge; Jahnke, Vanessa; Del Carmine, Peggy; Gondin, Julien; Arnould, David; Durieux, Anne Cécile; Freyssenet, Damien

    2017-09-07

    Sepsis induced loss of muscle mass and function contributes to promote physical inactivity and disability in patients. In this experimental study, mice were sacrificed 1, 4, or 7 days after cecal ligation and puncture (CLP) or sham surgery. When compared with diaphragm, locomotor muscles were more prone to sepsis-induced muscle mass loss. This could be attributed to a greater activation of ubiquitin-proteasome system and an increased myostatin expression. Thus, this study strongly suggests that the contractile activity pattern of diaphragm muscle confers resistance to atrophy compared to the locomotor gastrocnemius muscle. These data also suggest that a strategy aimed at preventing the activation of catabolic pathways and preserving spontaneous activity would be of interest for the treatment of patients with sepsis-induced neuromyopathy.

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

    Science.gov (United States)

    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

  13. 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.

  14. Innominate Vein Stenosis in Association with Ipsilateral Hyperdynamic Brachiobasilic Fistula Causing Ipsilateral Limb and Hemifacial Swelling.

    Science.gov (United States)

    Narendra, J B; Sreenivas, J; Karthikeyan, V S; Nagaraja, N H

    2017-01-01

    A 34-year-old hypertensive woman with a hyperdynamic, left brachiobasilic dialysis fistula presented with a long history of throbbing in her head and swelling of the left side of the face. Tight stenosis of left brachiocephalic vein was found to be causing retrograde flow into the left jugular vein which normalized after dilatation and stenting with resolution of all the symptoms and patient is asymptomatic for 1 year.

  15. Sepsis (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Sepsis KidsHealth / For Parents / Sepsis What's in this article? ... When to Call the Doctor Print What Is Sepsis? Sepsis is when the immune system responds to ...

  16. 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

  17. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis.

    Science.gov (United States)

    Chen, Ching-Wen; Mittal, Rohit; Klingensmith, Nathan J; Burd, Eileen M; Terhorst, Cox; Martin, Greg S; Coopersmith, Craig M; Ford, Mandy L

    2017-09-15

    Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8 + T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4 + T cells in septic animals and human patients at early time points. Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly increased survival in a murine cecal ligation and puncture model. Further, CD4-specific conditional knockouts showed that 2B4 functions on CD4 + T cell populations in a cell-intrinsic manner and modulates adaptive and innate immune responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory signaling on CD4 + T cells in mediating immune dysregulation. Copyright © 2017 by The American Association of Immunologists, Inc.

  18. Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis.

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves-de-Albuquerque

    Full Text Available Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA, a monounsaturated fatty acid (MUFA. We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP. OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A mRNA levels were increased, while uncoupling protein 2 (UCP2 liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA.

  19. Conserved Bacterial-Binding Peptides of the Scavenger-Like Human Lymphocyte Receptor CD6 Protect From Mouse Experimental Sepsis

    Directory of Open Access Journals (Sweden)

    Mario Martínez-Florensa

    2018-04-01

    Full Text Available Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW. All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Glucocorticoid resistance as a major drive in sepsis pathology.

    Science.gov (United States)

    Dendoncker, Karen; Libert, Claude

    2017-06-01

    Sepsis is an acute systemic inflammatory disease. Glucocorticoids (GCs), which function by binding to the GC receptor GR have very powerful anti-inflammatory activities, yet they are hardly useful in sepsis. We can thus consider sepsis as a GC resistant disease. We here review the literature which has investigated this GC resistance, and summarize the mechanisms of GC resistance that have been observed in other diseases and in experimental models. We also discuss the importance of GC resistance in sepsis, in terms of the contribution of this phenomenon to the pathogenesis of sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Hyperdynamic circulatory changes in liver cirrhosis: Comparative evaluation by doppler ultrasonography with normal subjects

    International Nuclear Information System (INIS)

    Im, Dae Wook; Baik, Soon Koo; Suh, Jung In; Kim, Jae Woo; Park, Yong Soon; Kim, Hyun Soo; Lee, Dong Ki; Kwon, Sang Ok

    2001-01-01

    To evaluate the cardiovascular and splanchnic hemodynamic changes in patients with liver cirrhosis and to compare with those of the normal controls using doppler ultrasonography. A total of 129 patients including 23 of Child-Pugh class A, 24 of class A, 24 of class B, 30 of class C, and 52 of the control group were included. Cardiac output (CO), systemic vascular resistance index (SVRI), and blood flow and pulsatility index (PI) of the superior mesenteric artery (SMA) were evaluated and compared among each groups. CO and SMA blood flow in the cirrhotic group were significantly higher than those in the control group, and the increase in CO and SMA blood flow showed a statistically significant correlation with the degree of liver dysfunction (p 2 =0.230). Hyperdynamic circulatory changes such as increases in CO and splanchnic blood flow were present in patients with liver cirrhosis. These changes may contribute to the development and maintenance of the portal hypertension due to an increase in portal blood flow an increase in portal blood flow.

  6. Polymer escape from a metastable Kramers potential: path integral hyperdynamics study.

    Science.gov (United States)

    Shin, Jaeoh; Ikonen, Timo; Khandkar, Mahendra D; Ala-Nissila, Tapio; Sung, Wokyung

    2010-11-14

    We study the dynamics of flexible, semiflexible, and self-avoiding polymer chains moving under a Kramers metastable potential. Due to thermal noise, the polymers, initially placed in the metastable well, can cross the potential barrier, but these events are extremely rare if the barrier is much larger than thermal energy. To speed up the slow rate processes in computer simulations, we extend the recently proposed path integral hyperdynamics method to the cases of polymers. We consider the cases where the polymers' radii of gyration are comparable to the distance between the well bottom and the barrier top. We find that, for a flexible polymers, the crossing rate (R) monotonically decreases with chain contour length (L), but with the magnitude much larger than the Kramers rate in the globular limit. For a semiflexible polymer, the crossing rate decreases with L but becomes nearly constant for large L. For a fixed L, the crossing rate becomes maximum at an intermediate bending stiffness. For the self-avoiding chain, the rate is a nonmonotonic function of L, first decreasing with L, and then, above a certain length, increasing with L. These findings can be instrumental for efficient separation of biopolymers.

  7. Hyperdynamic circulatory changes in liver cirrhosis: Comparative evaluation by doppler ultrasonography with normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Im, Dae Wook; Baik, Soon Koo; Suh, Jung In; Kim, Jae Woo; Park, Yong Soon; Kim, Hyun Soo; Lee, Dong Ki; Kwon, Sang Ok [Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of)

    2001-12-15

    To evaluate the cardiovascular and splanchnic hemodynamic changes in patients with liver cirrhosis and to compare with those of the normal controls using doppler ultrasonography. A total of 129 patients including 23 of Child-Pugh class A, 24 of class A, 24 of class B, 30 of class C, and 52 of the control group were included. Cardiac output (CO), systemic vascular resistance index (SVRI), and blood flow and pulsatility index (PI) of the superior mesenteric artery (SMA) were evaluated and compared among each groups. CO and SMA blood flow in the cirrhotic group were significantly higher than those in the control group, and the increase in CO and SMA blood flow showed a statistically significant correlation with the degree of liver dysfunction (p<0.01). SVRI and SMA PI reflecting vascular resistance in the cirrhotic group were significantly lower than those in the control group, and the decrease in SVRI and SMA PI also showed a statistically significant correlation with the degree of liver dysfunction (p<0.01). SMA blood flow showed a statistically significant inverse relationship with SMA PI (R{sup 2}=0.230). Hyperdynamic circulatory changes such as increases in CO and splanchnic blood flow were present in patients with liver cirrhosis. These changes may contribute to the development and maintenance of the portal hypertension due to an increase in portal blood flow an increase in portal blood flow.

  8. The release of endotoxin, TNF and IL-6 during the antibiotic treatment of experimental Gram-negative sepsis

    NARCIS (Netherlands)

    Dofferhoff, A.S.M.; Potthoff, H.; Bom, V.J.J.; Bartels, H.L.; De Vries-Hospers, H.G.; Bijzet, J.; Weits, J.; Buurman, W.; Bleichrodt, R.P.

    1995-01-01

    To evaluate the role of different antibiotics in the release of endotoxin and the production of tumor necrosis factor-α (TNF) and interleukin 6 (IL-6) during the treatment of experimental Escherichia coli septical peritonitis, we obtained serial blood samples from septic rats treated with placebo,

  9. Gamma-scintigraphy and early hepatocellular dysfunction during posttraumatic sepsis.

    Science.gov (United States)

    McGinty, M P; Stewart, R M; Fabian, M J; Fabian, T C; Proctor, K G

    1994-09-01

    To determine whether the hepatic conjugation-detoxification function was altered during sepsis, the metabolism of bilirubin was measured with gamma-scintigraphy. Time-activity curves were generated after a radiolabeled bilirubin analog (technetium 99m-mebrofenin, hepatoiminodiacetic acid [HIDA]) was administered to anesthetized (fentanyl) mongrel pigs in the following conditions: control (n = 16); 30 minutes after 5 micrograms/kg intravenous Escherichia coli endotoxin (LPS; n = 6); 30 minutes after trauma (40% arterial hemorrhage plus soft tissue injury, n = 9); 72 hours after sham trauma (n = 6); 72 hours after fluid resuscitated trauma either before (n = 9) or 30 minutes after (n = 10) LPS administration. All were ventilated with 65% O2 and instrumented with pulmonary artery oximetric catheters. After trauma plus LPS, the rate of HIDA uptake was depressed 20% to 30% (p trauma alone or LPS alone, uptake was not altered and elimination was prolonged less than twofold (p trauma alone (62 +/- 10), LPS alone (79 +/- 6), or trauma plus LPS (71 +/- 6) compared with control (102 +/- 5), sham (112 +/- 11), or pre-LPS (120 +/- 10) (p trauma or LPS alone or in combination. Changes in HIDA uptake-excretion within 30 minutes of LPS after resuscitated trauma coincided with neutropenia and pulmonary hypertension and preceded a hyperdynamic inflammatory state characterized by increased CI (194 +/- 19 ml/min/kg, p hepatic reserve and this occult dysfunction in the conjugation-detoxification system or bilirubin metabolism is unmasked by LPS; (2) hepatic dysfunction could have a role in the pathogenesis of the hyperdynamic circulatory response evoked by LPS because HIDA clearance was reduced before CI increased or systemic vascular resistance decreased; (3) HIDA clearance is a rapid, reliable, and inexpensive estimate of bilirubin metabolism that may have a practical application in patients with septic trauma or others with occult liver dysfunction.

  10. Virulence genes and subclone status as markers of experimental virulence in a murine sepsis model among Escherichia coli sequence type 131 clinical isolates from Spain.

    Directory of Open Access Journals (Sweden)

    Irene Merino

    Full Text Available To assess experimental virulence among sequence type 131 (ST131 Escherichia coli bloodstream isolates in relation to virulence genotype and subclone.We analysed 48 Spanish ST131 bloodstream isolates (2010 by PCR for ST131 subclone status (H30Rx, H30 non-Rx, or non-H30, virulence genes (VGs, and O-type. Then we compared these traits with virulence in a murine sepsis model, as measured by illness severity score (ISS and rapid lethality (mean ISS ≥ 4.Of the 48 study isolates, 65% were H30Rx, 21% H30 non-Rx, and 15% non-H30; 44% produced ESBLs, 98% were O25b, and 83% qualified as extraintestinal pathogenic E. coli (ExPEC. Of 49 VGs, ibeA and iss were associated significantly with non-H30 isolates, and sat, iha and malX with H30 isolates. Median VG scores differed by subclone, i.e., 12 (H30Rx, 10 (H30 non-Rx, and 11 (non-H30 (p < 0.01. Nearly 80% of isolates represented a described virotype. In mice, H30Rx and non-H30 isolates were more virulent than H30 non-Rx isolates (according to ISS [p = 0.03] and rapid lethality [p = 0.03], as were ExPEC isolates compared with non-ExPEC isolates (median ISS, 4.3 vs. 2.7: p = 0.03. In contrast, most individual VGs, VG scores, VG profiles, and virotypes were not associated with mouse virulence.ST131 subclone and ExPEC status, but not individual VGs, VG scores or profiles, or virotypes, predicted mouse virulence. Given the lower virulence of non-Rx H30 isolates, hypervirulence probably cannot explain the ST131-H30 clade's epidemic emergence.

  11. 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...

  12. Atrofia mucosa/translocação bacteriana na sepse experimental em ratos Wistar Mucosal atrophy/bacterial translocation in experimental sepsis in Wistar rats

    Directory of Open Access Journals (Sweden)

    Armando José d'Acampora

    2004-10-01

    jejunum were processed histologically for morphometric measure of the total thickness of the jejujum's wall in comparison to the thickness of the mucosa + submucosa layer. RESULTS: In blood culture, there was growth of Pseudomonas aeruginosa and Escherichia coli in 90% and 52,5% of the animals, respectively. In the peritoneal culture, there was growth of P aeruginosa, E.coli and Klebsiella sp in 87,5%, 85% and 5% of the animals. About the histological analysis and the thickness of the mucosa + submucosa's layer, there was not significant alteration. CONCLUSION: Acute sepsis did not develop any thickness alteration in the small intestine's mucosa layer. Bacterial translocation can not be a direct consequence produced by mucosal intestinal injury.

  13. Clinical management of sepsis.

    Science.gov (United States)

    Lam, S M; Lau, A Cw; Lam, R Pk; Yan, W W

    2017-06-01

    Sepsis is a common cause of hospital admission worldwide and contributes significantly to morbidity and mortality. The definition of sepsis has evolved from the 1991 American College of Chest Physicians/Society of Critical Care Medicine definition based on the criteria of systemic inflammatory response syndrome, to the 2016 Sepsis-3 definition that incorporates the Sequential Organ Failure Assessment score. The landmark trial on protocolised early goal-directed therapy was published in 2001, but three subsequent multicentre randomised controlled trials (ProCESS, ARISE, and ProMISe) in 2014-2015 did not confirm a survival benefit with protocolised care. Over the years, there has been considerable improvement in sepsis outcome and management that hinges on early detection; timely source control; prompt, appropriate, and correctly dosed antibiotics; aggressive fluid resuscitation; and shock reversal. These are all directed by repeated bedside assessment. This article summarises recent developments and landmark trials that should guide current sepsis management.

  14. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... 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...

  15. 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

  16. Sepsis and septic shock

    Science.gov (United States)

    Hotchkiss, Richard S.; Moldawer, Lyle L.; Opal, Steven M.; Reinhart, Konrad; Turnbull, Isaiah R.; Vincent, Jean-Louis

    2017-01-01

    For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental. PMID:28117397

  17. Sepsis: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Eliézer Silva

    2008-01-01

    Full Text Available Sepsis is a syndrome related to severe infections. It is defined as the systemic host response to microorganisms in previously sterile tissues and is characterized by end-organ dysfunction away from the primary site of infection. The normal host response to infection is complex and aims to identify and control pathogen invasion, as well as to start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to both anti-inflammatory and proinflammatory responses. The chain of events that leads to sepsis is derived from the exacerbation of these mechanisms, promoting massive liberation of mediators and the progression of multiple organ dysfunction. Despite increasing knowledge about the pathophysiological pathways and processes involved in sepsis, morbidity and mortality remain unacceptably high. A large number of immunomodulatory agents have been studied in experimental and clinical settings in an attempt to find an efficacious anti-inflammatory drug that reduces mortality. Even though preclinical results had been promising, the vast majority of these trials actually showed little success in reducing the overwhelmingly high mortality rate of septic shock patients as compared with that of other critically ill intensive care unit patients. Clinical management usually begins with prompt recognition, determination of the probable infection site, early administration of antibiotics, and resuscitation protocols based on "early-goal" directed therapy. In this review, we address the research efforts that have been targeting risk factor identification, including genetics, pathophysiological mechanisms and strategies to recognize and treat these patients as early as possible.

  18. New biomarkers for sepsis

    Directory of Open Access Journals (Sweden)

    Li-xin XIE

    2013-01-01

    Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.

  19. 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.

  20. 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/.

  1. Increased plasma zonulin in patients with sepsis.

    Science.gov (United States)

    Klaus, Daniel A; Motal, Michael C; Burger-Klepp, Ursula; Marschalek, Corinna; Schmidt, Elisabeth M; Lebherz-Eichinger, Diana; Krenn, Claus G; Roth, Georg A

    2013-01-01

    Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.

  2. Diagnosis and management of sepsis

    Science.gov (United States)

    Arifin

    2018-03-01

    Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.

  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. Inhibition of nitric oxide synthase in hyperdynamic circulation of rats with early or late cirrhosis secondary to common bile duct ligation

    International Nuclear Information System (INIS)

    Kato, Yoshihito; Katsuta, Yasumi; Zhang, Xue-Jun; Ohsuga, Masaru; Miyamoto, Akiko; Komeichi, Hirokazu; Shimizu, Shuji; Mizuno, Kyoichi; Akimoto, Toshio

    2011-01-01

    Preventing internal hemorrhage extends the lifespan of rats with chronic bile duct ligation (CBDL), a common animal model of portal hypertension. We investigated hemodynamics during the early and late stages of cirrhosis caused by CBDL. We also evaluated the hemodynamic influence of nitric oxide (NO), which is the chief vasodilator in hyperdynamic syndrome, by administration of an NO synthase inhibitor (N G -nitro-L-arginine methyl ester: L-NAME; 10 mg/kg). In 24 Sprague-Dawley rats (9 sham rats and 15 CBDL rats), hemodynamics were assessed under conscious and unrestrained conditions 4 and 8 weeks after surgery. Before and 30 minutes after L-NAME administration, the cardiac index (CI) and regional blood flow were measured with the reference sample method using 141 Ce- and 113 Sn-microspheres (15 μm in diameter). A hyperdynamic systemic circulation and splanchnic hyperemia were observed after CBDL, and these changes increased with the progression of cirrhosis. L-NAME significantly diminished the hyperdynamic circulation and also reduced splanchnic hyperemia. In 4-week CBDL rats, a low hemoglobin concentration made an important contribution to the hyperdynamic circulation, and the portal collateral system collapsed when inflow to the portal territory was reduced by L-NAME treatment. In 8-week CBDL rats, systemic hemodynamics were closely linked to both the splanchnic circulation and the renal circulation before and after L-NAME administration, apart from hepatic artery blood flow. The distinctive hemodynamic changes of portal hypertension were found in 8-week CBDL rats. Thus, 8-week CBDL rats may be a better animal model of human portal hypertension than 4-week CBDL rats. (author)

  5. 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.

  6. MICRONUTRIENT THERAPY FOR SEPSIS

    Directory of Open Access Journals (Sweden)

    Agung Prasetiyo

    2015-05-01

    Full Text Available Micronutrients are nutrients which are needed by the body to perform the function of body. The amounts is less than 100% μg per day and consist of vitamins and minerals. It cannot be synthesized in the body. Research in the US mentioned that the rate prevalence of sepsis is tended to be increased 8.7 % annually. In sepsis, nutrition is one of the important component which could drive the success treatment. Micronutrient, especially a vitamin which is soluble in fats, it would be toxic if the number exceed the capability of body to receive it. Although there are guidance and mutual agreement about sepsis using, it still need to concern on micronutrient which potentially giving bad effect. In sepsis case, micronutrients also determine the success of treatment due to redistribution of vitamin and trace element from circulation to the tissue which involved in the proteins formation and immune system. The conclusions of the latest 7 experiments and 4 random controlled studies of multi-centre support the micronutrients supplementation because it can decrease mortality rate. However, it still need to be aware to the toxicity of fat soluble micronutrient if the doses are excessive.

  7. Approach to neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Shankar Narayan

    2015-01-01

    The treatment includes supportive care along with administration of appropriate antibiotics. Adjuvant treatment includes IVIG, GCSF, exchange transfusion and pentoxifylline administration. This paper aims to present an algorithmic approach to neonatal sepsis to expedite the diagnosis along with providing appropriate and adequate treatment.

  8. Nitrogenoxid og sepsis

    DEFF Research Database (Denmark)

    El-Haj, Lama; Bestle, Morten Heiberg

    2018-01-01

    The main purpose of this study is to review the function of nitric oxide during sepsis and septic shock. Futhermore, the study reviews the various physiological functions of nitric oxide in the human body, and how these functions can and have been used clinically. Nitric oxide plays an important ...

  9. Sepsis Associated Encephalopathy

    Directory of Open Access Journals (Sweden)

    Neera Chaudhry

    2014-01-01

    Full Text Available Sepsis associated encephalopathy (SAE is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis.

  10. Inoculum effect on the efficacies of amoxicillin-clavulanate, piperacillin-tazobactam, and imipenem against extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli in an experimental murine sepsis model.

    Science.gov (United States)

    Docobo-Pérez, F; López-Cerero, L; López-Rojas, R; Egea, P; Domínguez-Herrera, J; Rodríguez-Baño, J; Pascual, A; Pachón, J

    2013-05-01

    Escherichia coli is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced in vitro activity in the presence of high concentrations of extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing E. coli bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical E. coli strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {~5.5 log10 CFU/g [low inoculum concentration (LI)] or ~7.5 log(10) CFU/g [high inoculum concentration (HI)]} using E. coli strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (-2.53 and -2.14 log10 CFU/g [P imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to -1.67 log10 CFU/g (P imipenem treatment of infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin-tazobactam.

  11. 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...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  12. 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...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  13. Unrevealing culture-negative severe sepsis

    OpenAIRE

    de Prost, Nicolas; Razazi, Keyvan; Brun-Buisson, Christian

    2013-01-01

    Sepsis involves a wide array of sources and microorganisms, only a fraction of which are microbiologically documented. Culture-negative sepsis poses special diagnostic challenges to both clinicians and microbiologists and further questions the validity of sepsis definitions.

  14. 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.

  15. 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

  16. Detoxification in Abdominal Sepsis

    Directory of Open Access Journals (Sweden)

    A. F. Potapov

    2005-01-01

    Full Text Available Objective. To comparatively analyze the efficiency of methods for extracorporeal detoxification (ED of the body in abdominal sepsis (AS and to choose the optimum detoxifying methods in relation to the level of endotoxicosis.Material and methods. 56 patients (41 males and 15 females; mean age 39.4±12.2 years with surgical abdominal infection of various genesis, complicated by the development of sepsis whose treatment included ED methods, were examined. The level of intoxication and the efficiency of detoxification were evaluated by general clinical and biochemical blood parameters, the leukocytic intoxication index, the levels of low and medium molecular-weight substances in the body’s media. Hemosorption, plasmapheresis, hemodialysis, hemodiafiltration, and hemofiltration were used for detoxification.Results. Surgical abdominal infection is accompanied by endotoxemia that has no clear nosological specificity, but it depends on the pattern of a clinical course of the disease and is most pronounced in the septic syndrome. In AS, 80.4% of the patients are observed to have an irreversible decompensation phase and a terminal degree of endotoxicosis, which require detoxification. The use of different ED methods according to the level of intoxication may reduce the level of endotoxicosis and yield a persistent beneficial effect in 85.2% of cases of its application. Conclusion. Filtration and dialysis techniques (hemodialysis, hemofiltration, and hemodiafiltration are the methods of choice in AS. Hemosorption and plasmapheresis may be recommended for use at the early stages of endotoxicosis development and in preserved renal excretory function.

  17. 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.

  18. Premise for Standardized Sepsis Models.

    Science.gov (United States)

    Remick, Daniel G; Ayala, Alfred; Chaudry, Irshad; Coopersmith, Craig M; Deutschman, Clifford; Hellman, Judith; Moldawer, Lyle; Osuchowski, Marcin

    2018-06-05

    Sepsis morbidity and mortality exacts a toll on patients and contributes significantly to healthcare costs. Preclinical models of sepsis have been used to study disease pathogenesis and test new therapies, but divergent outcomes have been observed with the same treatment even when using the same sepsis model. Other disorders such as diabetes, cancer, malaria, obesity and cardiovascular diseases have used standardized, preclinical models that allow laboratories to compare results. Standardized models accelerate the pace of research and such models have been used to test new therapies or changes in treatment guidelines. The National Institutes of Health (NIH) mandated that investigators increase data reproducibility and the rigor of scientific experiments and has also issued research funding announcements about the development and refinement of standardized models. Our premise is that refinement and standardization of preclinical sepsis models may accelerate the development and testing of potential therapeutics for human sepsis, as has been the case with preclinical models for other disorders. As a first step towards creating standardized models, we suggest 1) standardizing the technical standards of the widely used cecal ligation and puncture model and 2) creating a list of appropriate organ injury and immune dysfunction parameters. Standardized sepsis models could enhance reproducibility and allow comparison of results between laboratories and may accelerate our understanding of the pathogenesis of sepsis.

  19. Sepsis por shigella flexneri

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    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.

  20. Moraxella catarrhalis sepsis

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    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.

  1. Radiologic findings of neonatal sepsis

    International Nuclear Information System (INIS)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won; Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong

    1997-01-01

    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

  2. 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.

  3. [Nutritional support in sepsis].

    Science.gov (United States)

    Ortiz Leyba, C; López Martínez, J; Blesa Malpica, A L

    2005-06-01

    Although it is considered that metabolic and nutritional support must be part of the management of septic patients, it has not been conclusively shown that nutritional support will improve survival or complications from sepsis. Specific data on this issue are scarce since there are few studies that have investigated specialized nutritional support in septic patients. Thus, most of the recommendations are based on outcomes obtained in severely ill patients with different pathologies. It is assumed that nutritional support should be carried out through the enteral route whenever possible, as in other critically ill patients. The energetic waste in these patients is highly variable, although in general terms the hypermetabolic situation may be classified as moderate. An adjustment factor of 1.25-1.30 is recommended for the Harris-Benedict's equation to calculate the caloric intake. Septic patients should receive a hyperproteic intake. The amount of glucose administered should not exceed 70% of non-protein calories, and lipids intake should not exceed 40%. With regards to micronutrients, it is recommended to increase the supply of those with antioxidant properties (vitamin E, carotenes, vitamin C, selenium). There are data to consider that the use of diets enriched with pharmaco-nutrients (both with parenteral and enteral routes) may be beneficial in septic patients, although there is some controversy when interpreting the outcomes.

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

    Directory of Open Access Journals (Sweden)

    Franciele do Nascimento Santos

    2014-10-01

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

  6. What?s New in Paediatric Sepsis

    OpenAIRE

    Farrell, Deborah; Nadel, Simon

    2016-01-01

    Severe sepsis and septic shock remains a leading cause of mortality and morbidity in children. There is ongoing uncertainty regarding the optimal treatment pathways however the initial management of sepsis is crucial. This article is designed to be an informal and personal review of recent developments in paediatric sepsis over the past 3?years.

  7. Role of microRNAs in sepsis.

    Science.gov (United States)

    Kingsley, S Manoj Kumar; Bhat, B Vishnu

    2017-07-01

    MicroRNAs have been found to be of high significance in the regulation of various genes and processes in the body. Sepsis is a serious clinical problem which arises due to the excessive host inflammatory response to infection. The non-specific clinical features and delayed diagnosis of sepsis has been a matter of concern for long time. MicroRNAs could enable better diagnosis of sepsis and help in the identification of the various stages of sepsis. Improved diagnosis may enable quicker and more effective treatment measures. The initial acute and transient phase of sepsis involves excessive secretion of pro-inflammatory cytokines which causes severe damage. MicroRNAs negatively regulate the toll-like receptor signaling pathway and regulate the production of inflammatory cytokines during sepsis. Likewise, microRNAs have shown to regulate the vascular barrier and endothelial function in sepsis. They are also involved in the regulation of the apoptosis, immunosuppression, and organ dysfunction in later stages of sepsis. Their importance at various levels of the pathophysiology of sepsis has been discussed along with the challenges and future perspectives. MicroRNAs could be key players in the diagnosis and staging of sepsis. Their regulation at various stages of sepsis suggests that they may have an important role in altering the outcome associated with sepsis.

  8. T-cell proliferative responses following sepsis in neonatal rats.

    Science.gov (United States)

    Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

    2003-01-01

    Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

  9. 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

  10. 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

  11. 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.

  12. Sepsis is a preventable public health problem.

    Science.gov (United States)

    Kempker, Jordan A; Wang, Henry E; Martin, Greg S

    2018-05-06

    There is a paradigm shift happening for sepsis. Sepsis is no longer solely conceptualized as problem of individual patients treated in emergency departments and intensive care units but also as one that is addressed as public health issue with population- and systems-based solutions. We offer a conceptual framework for sepsis as a public health problem by adapting the traditional model of primary, secondary, and tertiary prevention.

  13. Advances in sepsis-associated liver dysfunction

    OpenAIRE

    Wang, Dawei; Yin, Yimei; Yao, Yongming

    2014-01-01

    Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS), and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs), hepatocytes and liver sinusoidal endothelial cells (LSECs). In additi...

  14. Advances in sepsis-associated liver dysfunction

    Directory of Open Access Journals (Sweden)

    Dawei Wang

    2014-07-01

    Full Text Available Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS, and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs, hepatocytes and liver sinusoidal endothelial cells (LSECs. In addition, activated neutrophils, which are also recruited to the liver and produce potentially destructive enzymes and oxygen-free radicals, may further enhance acute liver injury. The clinical manifestations of sepsis-associated liver dysfunction can roughly be divided into two categories: Hypoxic hepatitis and jaundice. The latter is much more frequent in the context of sepsis. Hepatic failure is traditionally considered as a late manifestation of sepsis-induced multiple organ dysfunction syndrome. To date, no specific therapeutics for sepsis-associated liver dysfunction are available. Treatment measure is mainly focused on eradication of the underlying infection and management for severe sepsis. A better understanding of the pathophysiology of liver response in sepsis may lead to further increase in survival rates.

  15. 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

  16. 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.

  17. I costi della sepsi in Italia

    Directory of Open Access Journals (Sweden)

    C. Lucioni

    2001-09-01

    Full Text Available The aim of this study is to evaluate additional hospitalisation costs and intangible costs (mortality in patients with sepsis (intended as severe sepsis or sepsis shock in Italy. The evaluation is based on clinical data from the Italian Sepsis Study, a prospective, multicentre study conducted in 99 Intensive Care Units (ICUslocated across Italy. Each ICU enrolled the first two (or three patients admitted each month, during the year April 1993 to March 1994. In particular, data collected included the Average Length Of Stay (ALOS in ICU and later in the regular ward, and the mortality within four weeks and in hospital. Out of the 2,946 patients enrolled, 2,641 never developed sepsis and were considered as the control group (comparability was confirmed based on gender, age, and comorbidity. The additional (respective to the control group ALOSs of the patients with sepsis were valued in monetary terms using per diem full costs, inflated to 2000: 1,033.43 Euro for l day in ICU (published data and 299.54 Euro for l day in the regular ward (estimated data based on published materials. Statistical significance was tested with Student t test. The hospitalisation cost of a patient with sepsis (21,571.88 Euro is significantly higher (+86% than that patient without sepsis (11,590.84 Euro, due to a longer (+ 163% stay in the expensive ICU, not balanced by shorter stay in the regular ward. Also intangible costs are significantly higher: the risk for an ICU patient with sepsis to die in hospital is 3 times higher than that of an ICU patient without sepsis. In particular, those patients developing sepsis after admission are more costly and with a higher mortality risk.

  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. 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

  20. 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 endotoxin-induced sepsis had an infusion rate of 2.2 mg/kg/hr (S.D. 0.5) for propofol and 12 microg/kg/hr (S.D. 2) for fentanyl, whereas...

  1. 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

  2. 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.

  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. Age, exercise, and the outcome of sepsis.

    Science.gov (United States)

    Banerjee, Debasree; Opal, Steven M

    2017-11-23

    We report on the increasingly important need to diagnose and care for the elderly with sepsis as a distinct patient population. We share an overview of age-related changes in sepsis physiology and the potential role of exercise.See related research by Tyml et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1783-1.

  6. Radiodiagnosis of lung syndrome in surgical sepsis

    International Nuclear Information System (INIS)

    Dvojnykh, V.P.; Palagin, E.K.

    1991-01-01

    The results of treatment of 23 patients with acute surgical sepsis were analysed. It was shown that the X-ray examination must be obligatory in surveillance of patients with purulent foci. Two roentgenological variants are possible in surgical sepsis: central and perepheric. X-ray examinations of chest organs should be conducted every 2-3 day

  7. A Sepsis-related Diagnosis Impacts Interventions and Predicts Outcomes for Emergency Patients with Severe Sepsis.

    Science.gov (United States)

    Kim, Mitchell; Watase, Taketo; Jablonowski, Karl D; Gatewood, Medley O; Henning, Daniel J

    2017-10-01

    Many patients meeting criteria for severe sepsis are not given a sepsis-related diagnosis by emergency physicians (EP). This study 1) compares emergency department (ED) interventions and in-hospital outcomes among patients with severe sepsis, based on the presence or absence of sepsis-related diagnosis, and 2) assesses how adverse outcomes relate to three-hour sepsis bundle completion among patients fulfilling severe sepsis criteria but not given a sepsis-related diagnosis. We performed a retrospective cohort study using patients meeting criteria for severe sepsis at two urban, academic tertiary care centers from March 2015 through May 2015. We included all ED patients with the following: 1) the 1992 Consensus definition of severe sepsis, including two or more systemic inflammatory response syndrome criteria and evidence of organ dysfunction; or 2) physician diagnosis of severe sepsis or septic shock. We excluded patients transferred to or from another hospital and those <18 years old. Patients with an EP-assigned sepsis diagnosis created the "Physician Diagnosis" group; the remaining patients composed the "Consensus Criteria" group. The primary outcome was in-hospital mortality. Secondary outcomes included completed elements of the current three-hour sepsis bundle; non-elective intubation; vasopressor administration; intensive care unit (ICU) admission from the ED; and transfer to the ICU in < 24 hours. We compared proportions of each outcome between groups using the chi-square test, and we also performed a stratified analysis using chi square to assess the association between failure to complete the three-hour bundle and adverse outcomes in each group. Of 418 patients identified with severe sepsis we excluded 54, leaving 364 patients for analysis: 121 "Physician Diagnosis" and 243 "Consensus Criteria." The "Physician Diagnosis" group had a higher in-hospital mortality (12.4% vs 3.3%, P < 0.01) and compliance with the three-hour sepsis bundle (52.1% vs 20.2%, P

  8. Hemostasis and endothelial damage during sepsis.

    Science.gov (United States)

    Johansen, Maria Egede

    2015-08-01

    The sepsis syndrome represents a disease continuum, including severe sepsis and septic shock associated with high mortality. One of the main problems in severe sepsis and septic shock, resulting in organ failure and death, are disturbances in the hemostasis due to sepsis-related coagulopathy. Sepsis-related coagulopathy affects not only traditional coagulation factors, but also the platelets and endothelium. Functional testing of the hemostatic system has found application in critical illness. Thrombelastography (TEG) provides an overview of the hemostatic system allowing for an evaluation of interactions between coagulation factors and platelets. Additionally, the role of the endothelium during sepsis can be explored through testing of biomarkers of endothelial damage. The three studies comprising this PhD thesis all investigate important aspects of the disturbed hemostasis during sepsis, including endothelial damage. Together, the specific findings from the three studies improve the existing understanding of sepsis-related coagulopathy, and the possible influences of some of the treatments offered these patients. The first study investigates the occurrence of antimicrobial-induced thrombocytopenia among critically ill patients. In sepsis, thrombocytopenia is a predictor of poor outcome, and reports, of mainly casuistic nature, have previously hypothesized that specific antimicrobial agents could induce in sepsis-related thrombocytopenia. This hypothesis was tested using a randomized designed set-up, encompassing 1147 critically ill patients, and no significant difference in risk of thrombocytopenia was observed among patients receiving large amounts of antimicrobials vs. patients receiving standard-of-care. As a consequence, the risk of antimicrobial-induced thrombocytopenia in the general population of critically ill patients seemingly does not represent a substantial problem and thrombocytopenia during critical illness is most likely due to other factors such

  9. From traditional biochemical signals to molecular markers for detection of sepsis after burn injuries.

    Science.gov (United States)

    Muñoz, Balam; Suárez-Sánchez, Rocío; Hernández-Hernández, Oscar; Franco-Cendejas, Rafael; Cortés, Hernán; Magaña, Jonathan J

    2018-05-22

    Sepsis is a life-threatening organ-dysfunction condition caused by a dysregulated response to an infectious condition that can cause complications in patients with major trauma. Burns are one of the most destructive forms of trauma; despite the improvements in medical care, infections remain an important cause of burn injury-related mortality and morbidity, and complicated sepsis predisposes patients to diverse complications such as organ failure, lengthening of hospital stays, and increased costs. Accurate diagnosis and early treatment of sepsis may have a beneficial impact on clinical outcome of burn-injured patients. In this review, we offer a comprehensive description of the current and traditional markers used as indicative of sepsis in burned patients. However, although these are markers of the inflammatory post-burn response, they usually fail to predict sepsis in severely burned patients due to that they do not reflect the severity of the infection. Identification and measurement of biomarkers in early stages of infection is important in order to provide timely response and effective treatment of burned patients. Therefore, we compiled important experimental evidence, demonstrating novel biomarkers, including molecular markers such as genomic DNA variations, alterations of transcriptome profiling (mRNA, miRNAs, lncRNAs and circRNAs), epigenetic markers, and advances in proteomics and metabolomics. Finally, this review summarizes next-generation technologies for the identification of markers for detection of sepsis after burn injuries. Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.

  10. Physicians’ and nurses‘ knowledge and attitudes in management of sepsis: An Italian study

    Directory of Open Access Journals (Sweden)

    Gabriella Nucera

    2018-03-01

    Full Text Available Introduction: Sepsis is one of the most deadly and costly conditions at hospitals. Our study aimed to study levels of knowledge and attitudes in management of sepsis among nurses and physicians employed at Fatebenefratelli hospital, Milano, North-Italy, with particular regard to the analysis of the effects of educational training. Methods: A cross-sectional, quasi-experimental study was conducted between June 1 and October 30, 2017. Physicians and nurses from Intensive Care Unit (ICU and non-ICU hospital wards were recruited. The study participants were invited to attend some educational workshops and, after 6 months, to fill out a questionnaire based on the 2016 Surviving Sepsis Campaign guidelines. Descriptive statistics were expressed with frequency and percentage (%. Chi-square and Student’s t-test were performed to compare the differences in awareness and knowledge between groups. P-values 75% of knowledge of procedures that increase risk of sepsis, ‘fairly‘ (50-75% levels of knowledge, attitudes and behaviour towards blood culture techniques, and ‘poor’ ( 1 years or never trained (34.8 ± 7.4% nurses (n = 99 and physicians (n = 30 (t(10 = 11.72, P = < 0.001. Discussion and Conclusion: Our findings showed that levels of knowledge concerning methods and scores for early identification of sepsis can be significantly improved by educational training. A good knowledge of sepsis guidelines is essential to correct management of this condition.

  11. 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.

  12. An international sepsis survey: a study of doctors' knowledge and perception about sepsis

    Science.gov (United States)

    Poeze, Martijn; Ramsay, Graham; Gerlach, Herwig; Rubulotta, Francesca; Levy, Mitchel

    2004-01-01

    Background To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis. Methods The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients. Results The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition. Conclusion There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently. PMID:15566585

  13. Sepsis

    Science.gov (United States)

    ... that may be done include: Blood differential Blood gases Kidney function tests Platelet count and fibrin degradation ... 2018, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  14. 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

  15. Is hypertriglyceridemia a prognostic factor in sepsis?

    Directory of Open Access Journals (Sweden)

    Cetinkaya A

    2014-02-01

    Full Text Available Ali Cetinkaya,1 Abdulsamet Erden,1 Deniz Avci,1 Hatice Karagoz,1 Samet Karahan,1 Mustafa Basak,1 Kadir Bulut,1 Vedat Gencer,1 Hasan Mutlu2 1Internal Medicine Department, Kayseri Training and Research Hospital, Kayseri, Turkey; 2Medical Oncology Department, Acibadem Kayseri Hospital, Kayseri, Turkey Introduction: Sepsis and septic shock are important causes of mortality in intensive care unit patients, hence early diagnosis and therapy are important in management of their treatment. The available information on sepsis patients is not enough to recommend or to discard the routine evaluation of triglyceride (TG levels at the onset of sepsis. The aim of this study was to investigate the association of hypertriglyceridemia and clinical outcome (or mortality in patients with severe sepsis. Materials and methods: Between January 1 and December 31, 2011, a total of 84 patients with sepsis from the intensive internal care unit at the Kayseri Training and Research Hospital, Kayseri, Turkey, were investigated retrospectively. Sepsis was defined according to the American College of Chest Physicians/Society of Critical Care Medicine/European Society of Intensive Care Medicine consensus conference definitions. For each patient, survival was recorded at the end of the last day of hospitalization as dead or alive. The TG values were taken retrospectively from the records, which were performed routinely for each patient with sepsis at the time of diagnosis. TG >150 mg/dL was considered as hypertriglyceridemia. Results: The percentages of male and female patients were 44% and 56%, respectively. The mean age of patients was 71.49±11.071 years. The percentage of patients with TG values more than 150 mg/dL was 81% (25/31 in the non-survivor group and 19% (6/31 in the survivor group. There was a significant difference regarding TG values between groups (P=0.039. Discussion: It was observed in this study that patients in the intensive care unit with sepsis had high

  16. The intestinal microenvironment in sepsis.

    Science.gov (United States)

    Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

    2017-10-01

    The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

  17. 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.

  18. Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis.

    Science.gov (United States)

    Pedrazza, Leonardo; Pereira, Talita Carneiro Brandão; Abujamra, Ana Lucia; Nunes, Fernanda Bordignon; Bogo, Maurício Reis; de Oliveira, Jarbas Rodrigues

    2017-07-01

    Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues. Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10 6 cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR. We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group. In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

  19. Seeking Sepsis in the Emergency Department- Identifying Barriers to Delivery of the Sepsis 6.

    Science.gov (United States)

    Bentley, James; Henderson, Susan; Thakore, Shobhan; Donald, Michael; Wang, Weijie

    2016-01-01

    The Sepsis 6 is an internationally accepted management bundle that, when initiated within one hour of identifying sepsis, can reduce morbidity and mortality. This management bundle was advocated by the Scottish Patient Safety Programme as part of its Acute Adult campaign launched in 2008 and adopted by NHS Tayside in 2012. Despite this, the Emergency Department (ED) of Ninewells Hospital, a tertiary referral centre and major teaching hospital in Scotland, was displaying poor success in the Sepsis 6. We therefore set out to improve compliance by evaluating the application of all aspects of the NHS Tayside Sepsis 6 bundle within one hour of ED triage time, to identify what human factors may influence achieving the one hour The Sepsis 6 bundle. This allowed us to tailor a number of specific interventions including educational sessions, regular audit and personal feedback and check list Sepsis 6 sticker. These interventions promoted a steady increase in compliance from an initial rate of 51.0% to 74.3%. The project highlighted that undifferentiated patients create a challenge in initiating the Sepsis 6. Pyrexia is a key human factor-trigger for recognising sepsis with initial nursing assessment being vital in recognition and identifying the best area (resus) of the department to manage severely septic patients. EDs need to recognise these challenges and develop educational and feedback plans for staff and utilise available resources to maximise the Sepsis 6 compliance.

  20. 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

  1. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    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...... on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation....

  2. 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....

  3. Procalcitonin ? Assisted Antibiotic Strategy in Sepsis

    OpenAIRE

    Tr?sy, Domonkos; Moln?r, Zsolt

    2017-01-01

    Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help f...

  4. 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.

  5. Regulators of Intestinal Epithelial Migration in Sepsis.

    Science.gov (United States)

    Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

    2018-02-08

    The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

  6. 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

  7. Anaesthetic management of patients with severe sepsis.

    Science.gov (United States)

    Eissa, D; Carton, E G; Buggy, D J

    2010-12-01

    Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

  8. 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

    2016-02-23

    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. To evaluate and, as needed, update definitions for sepsis and septic shock. 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). 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. 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 greater risk of mortality than with sepsis alone. Patients with septic shock

  9. A prospective treatment for sepsis

    Directory of Open Access Journals (Sweden)

    Shahidi Bonjar MR

    2015-05-01

    Full Text Available Mohammad Rashid Shahidi Bonjar,1 Leyla Shahidi Bonjar2 1School of Dentistry, 2College of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran Abstract: The present paper proposes a prospective auxiliary treatment for sepsis. There exists no record in the published media on the subject. As an auxiliary therapy, efficacious extracorporeal removal of sepsis-causing bacterial antigens and their toxins (BATs from the blood of septic patients is discussed. The principal component to this approach is a bacterial polyvalent antibody-column (BPVAC, which selectively traps wide spectrum of BATs from blood in an extracorporeal circuit, and detoxified blood returns back to the patient’s body. BPVAC treatment would be a device of targeted medicine. Detoxification is performed under supervision of trained personnel using simple blood-circulating machines in which blood circulates from the patient to BPVAC and back to the patient aseptically. BPVACs’ reactive sites consist of carbon nanotubes on which a vast spectra of polyvalent BATs-antibodies are bond to. The devise acts as a biological filter that selectively immobilizes harmful BATs from intoxicated blood; however, no dialysis is involved. For effective neutralization, BPVAC provides large contact surface area with blood. BPVAC approach would have advantages of: 1 urgent neutralization of notorious BATs from blood of septic patients; 2 applicability in parallel with conventional treatments; 3 potential to minimize side effects of the malady; 4 applicability for a vast range of BATs; 5 potential to eliminate contact of BATs with internal tissues and organs; 6 tolerability by patients sensitive to antiserum injections; 7 capability for universal application; 8 affectivity when antibiotic-resistant bacteria are involved and the physician has no or limited access to appropriate antibiotics; and 10 being a single-use, disposable, and stand-alone device. Before using it for clinical trials in

  10. 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

  11. Pregnancy-associated severe sepsis.

    Science.gov (United States)

    Oud, Lavi

    2016-04-01

    This article examines the contemporary knowledge and uncertainties about the burden of pregnancy-associated severe sepsis (PASS), and its manifestations, management, and outcomes. There are relatively sparse data on PASS, related in part to infrequent reports and varying use of terminology and case definitions. PASS remains rare, although its incidence appears to be rapidly rising in some high-resource countries, affecting especially women with limited resources, minorities, and those with chronic illness. High level of clinician vigilance and rapid initiation of appropriate antimicrobial therapy, coupled with effective systemic support for organ dysfunction and correction of occult and overt hypoperfusion are the keys to limit adverse outcomes. However, timely diagnosis and provision of effective care remain a challenge, with reported prevalent delay in recognition and delivery of time-sensitive care interventions among maternal decedents. The mortality rate of PASS has been rising and its case fatality, although relatively low, has remained unchanged, in contrast to the outcome gains in the general population. The long-term sequelae of PASS remain unknown. The relatively limited contemporary data on PASS suggest a rising public health hazard in the obstetric population in high-resource countries, with ongoing challenges in assuring consistent provision of time-sensitive care.

  12. The aPC treatment improves microcirculation in severe sepsis/septic shock syndrome

    NARCIS (Netherlands)

    Donati, Abele; Damiani, Elisa; Botticelli, Laura; Adrario, Erica; Lombrano, Maria Rita; Domizi, Roberta; Marini, Benedetto; van Teeffelen, Jurgen W. G. E.; Carletti, Paola; Girardis, Massimo; Pelaia, Paolo; Ince, Can

    2013-01-01

    The role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the

  13. Much Ado About the New Definitions of Sepsis

    Directory of Open Access Journals (Sweden)

    Copotoiu Sanda-Maria

    2016-04-01

    Full Text Available Following the publication of the new definition of sepsis (Sepsis-3, a plethora of articles have been published in medical journals. Recognizing the epidemiological importance of the previous definitions, first issued in 1992 (Sepsis-1, and subsequently revised in 2001 (Sepsis-2, the most recent opinion emphasizes the failure “to provide adequate groups of patients with homogenous aetiologies, presentations and outcomes”, and blamed one of the causes “for the failure of several randomized controlled trials (RCTs, that tested the efficacy of adjuvant sepsis therapies”. This review summarizes the recent advances in sepsis definition.

  14. 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.

  15. Post–Acute Care Use and Hospital Readmission after Sepsis

    Science.gov (United States)

    Jones, Tiffanie K.; Fuchs, Barry D.; Small, Dylan S.; Halpern, Scott D.; Hanish, Asaf; Umscheid, Craig A.; Baillie, Charles A.; Kerlin, Meeta Prasad; Gaieski, David F.

    2015-01-01

    Rationale: The epidemiology of post–acute care use and hospital readmission after sepsis remains largely unknown. Objectives: To examine the rate of post–acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis. Methods: In an observational cohort study conducted in an academic health care system (2010–2012), we compared post–acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis. Measurements and Main Results: Post–acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P Readmission rates at 7, 30, and 90 days were higher postsepsis (P readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0–26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38–1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. Conclusions: Post–acute care use and hospital readmissions were common after sepsis. The increased readmission risk after sepsis was observed regardless of sepsis severity and was associated with adverse readmission outcomes. PMID:25751120

  16. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    Science.gov (United States)

    Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

    2016-07-01

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

  17. Plasminogen activators in inflammation and sepsis.

    Science.gov (United States)

    Pechlaner, Ch

    2002-01-01

    Mortality of severe sepsis remains at 40% to 50%. Intensive efforts over the past two decades have only marginally improved outcome. Improving outcome in sepsis depends on understanding its pathophysiology, which involves triggers, responses of the organism, and dysfunction. Stress, injury, or infection trigger host responses, including local and systemic orchestrated mechanisms. Dysfunction and outcome depend on both trigger and response. Blood coagulation, inflammation, immunity, and fibrinolysis are critical components of the organism's responses. Understanding their role in sepsis pathophysiology is the key to effective treatment. Relevant studies were identified by a systematic literature search, complemented by manual search of individual citations. Using PubMed, 'sepsis' yields more than 62,000 references, 'plasminogen activators' more than 21,000. The selection of citations was guided by preference for reviews that expand important threads of argumentation. Single original studies were included when relevant to critical points. This analytical review describes the essential elements of pathophysiology and the current status of sepsis treatment. Based on this context, an emerging therapeutic option will be discussed: plasminogen activators.

  18. Improving Outcomes in Patients With Sepsis.

    Science.gov (United States)

    Armen, Scott B; Freer, Carol V; Showalter, John W; Crook, Tonya; Whitener, Cynthia J; West, Cheri; Terndrup, Thomas E; Grifasi, Marissa; DeFlitch, Christopher J; Hollenbeak, Christopher S

    2016-01-01

    Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. © The Author(s) 2014.

  19. 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

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

    African Journals Online (AJOL)

    management of sepsis has resulted in a remarkable increase of new knowledge on the ... As sepsis progresses to septic shock, the risk of dying increases substantially. Where .... altered mental state, thrombocytopenia, raised serum lactate ...

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

    African Journals Online (AJOL)

    TOSHIBA

    Relationship between outcome variable and exposure variable was done using Chi ... A recent study in Ethiopia indicates that neonatal sepsis in the major newborn ... Neonatal sepsis was defined as infection that had occurred during the.

  2. Attenuation of sepsis-induced rat liver injury by epigallocatechin ...

    African Journals Online (AJOL)

    rat model of sepsis established by cercal ligation and puncture (CLP). Methods: Male Wistar ... capacity, resulting in excessive oxidants in cells. [6]. ... Care (NIH publication no. 85-23 ..... estimates of severe sepsis in United States emergency.

  3. 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....

  4. 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.

  5. 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.

  6. Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management.

    Science.gov (United States)

    Taeb, Abdalsamih M; Hooper, Michael H; Marik, Paul E

    2017-06-01

    Sepsis is a clinical syndrome that results from the dysregulated inflammatory response to infection that leads to organ dysfunction. The resulting losses to society in terms of financial burden, morbidity, and mortality are enormous. We provide a review of sepsis, its underlying pathophysiology, and guidance for diagnosis and management of this common disease. Current established treatments include appropriate antimicrobial agents to target the underlying infection, optimization of intravascular volume to improve stroke volume, vasopressors to counteract vasoplegic shock, and high-quality supportive care. Appropriate implementation of established treatments combined with novel therapeutic approaches promises to continue to decrease the impact of this disease.

  7. Indium 111 leucocyte scintigraphy in abdominal sepsis

    International Nuclear Information System (INIS)

    Baba, A.A.; McKillop, J.H.; Gray, H.W.; Cuthbert, G.F.; Neilson, W.; Anderson, J.R.

    1990-01-01

    We have studied the clinical utility of indium 111 autologous leucocyte scintigraphy retrospectively in 45 patients presenting with suspected intra-abdominal sepsis. The sensitivity was 95% (21/22) and the specificity was 91% (21/23). Some 34 of the studies (17 positive and 17 negative) were considered helpful in furthering patient management (76%) and 8, unhelpful (18%). In 3, the study results were misleading and led to inappropriate treatment. Indium 111 scintigraphy, whether positive or negative, provides information in patients with suspected intra-abdominal sepsis upon which therapeutic decisions can be based. (orig.)

  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. 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 ...

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. Pulmonary dynamics of radiolabelled erythrocytes and leucocytes in early gram-negative sepsis in pigs

    International Nuclear Information System (INIS)

    Walther, Sten; Wenyao, Shi; Lennquist, Sten

    1999-01-01

    objective: to study the pulmonary dynamic of erythrocytes and leucocytes in vivo in early experimental sepsis. design: open, experimental study. setting: academic research laboratory, Sweden. material: 10 adolescent, domestic pigs. interventions: technetium (Tc 99) labelling of erythrocytes (n=5) and indium (In 111) labelling of autologous leucocytes (n=10). sepsis was induced by endotoxin (n=4) or live Escherichia Coli (n=3), given intravenously. major outcome measures: regional pulmonary scintigraphy, central haemodynamics and gas exchange followed for 180 minutes. results: septic animals developed arterial hypoxia, pulmonary hypertension and systemic hypotension. They also had an early increase in mean (SD) regional pulmonary erythrocyte and leucocyte counts (+10.3(7.7%) and + 12.0 (3.5%) respectively) with simultaneous maximum 27-32 minutes after the start of the septic insult. Conclusions: The immediate sepsis-induced pulmonary accumulation of leucocytes as detected by external scintigraphy can be ascribed at least in part, to a simultaneous sepsis-induced increase in pulmonary blood volume. 3 figs., 1 tab., 19 refs

  17. Polarization of microglia and its role in bacterial sepsis.

    Science.gov (United States)

    Michels, Monique; Sonai, Beatriz; Dal-Pizzol, Felipe

    2017-02-15

    Microglial polarization in response to brain inflammatory conditions is a crescent field in neuroscience. However, the effect of systemic inflammation, and specifically sepsis, is a relatively unexplored field that has great interest and relevance. Sepsis has been associated with both early and late harmful events of the central nervous system, suggesting that there is a close link between sepsis and neuroinflammation. During sepsis evolution it is supposed that microglial could exert both neurotoxic and repairing effects depending on the specific microglial phenotype assumed. In this context, here it was reviewed the role of microglial polarization during sepsis-associated brain dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Neutrophil migration under normal and sepsis conditions.

    Science.gov (United States)

    Lerman, Yelena V; Kim, Minsoo

    2015-01-01

    Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.

  19. Sepsis progression and outcome: a dynamical model

    Directory of Open Access Journals (Sweden)

    Gessler Damian DG

    2006-02-01

    Full Text Available Abstract Background Sepsis (bloodstream infection is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis progression, based upon basic physiologic principles, which could eventually guide hourly treatment decisions. Results We present an initial mathematical model of sepsis, based on metabolic rate theory that links basic vascular and immunological dynamics. The model includes the rate of vascular circulation, a surrogate for the metabolic rate that is mechanistically associated with disease progression. We use the mass-specific rate of blood circulation (SRBC, a correlate of the body mass index, to build a differential equation model of circulation, infection, organ damage, and recovery. This introduces a vascular component into an infectious disease model that describes the interaction between a pathogen and the adaptive immune system. Conclusion The model predicts that deviations from normal SRBC correlate with disease progression and adverse outcome. We compare the predictions with population mortality data from cardiovascular disease and cancer and show that deviations from normal SRBC correlate with higher mortality rates.

  20. Procalcitonin - Assisted Antibiotic Strategy in Sepsis.

    Science.gov (United States)

    Trásy, Domonkos; Molnár, Zsolt

    2017-05-01

    Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help fast and accurate diagnosis biomarkers have been measured for decades. Procalcitonin (PCT) is one of the most studied, but the results are conflicting. Sepsis means a very loose cohort of a large heterogeneous patient population, hence defining certain cut off values for PCT to differentiate between different severities of the disease is almost impossible. Clinicians first have to understand the pathophysiological background of sepsis to be able to interpret correctly the PCT results. Nevertheless, PCT has been shown to have the best sensitivity and specificity to indicate infection, antibiotic appropriateness and stopping therapy. In this article we will focus on some important aspects of pathophysiology and advice on how to implement that in the everyday clinical practice. We believe that this multimodal evaluation of the clinical picture together with PCT results can be a useful tool to make the most out of the PCT results, and do the best for patients on the ICU.

  1. Diagnostic value of procalcitonin in neonatal sepsis

    African Journals Online (AJOL)

    2015-04-27

    Apr 27, 2015 ... Abstract: Introduction: Neonatal sepsis is a major cause of mortal- ity in developing countries. Accu- rate and quick diagnosis are diffi- cult because clinical presentation are non-specific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. Serum procalci-.

  2. [Pharmaconutrition with parenteral selenium in sepsis].

    Science.gov (United States)

    Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

    2014-04-01

    Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  3. 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...

  4. Immunotolerance during bacterial pneumonia and sepsis

    NARCIS (Netherlands)

    Hoogerwerf, J.J.

    2010-01-01

    Bacterial pneumonia and sepsis are a major cause of morbidity and mortality worldwide. Massive use of antibiotics promotes pathogen resistance, and, as a consequence, the incidence of drug-resistant bacteria is increasing. Therefore, it is of the utmost importance to expand our comprehension of host

  5. The effect of bacterial sepsis severity on triglyceride value

    Science.gov (United States)

    Fahila, R.; Kembaren, T.; Rahimi, A.

    2018-03-01

    Sepsis can increase the amount of triglyceride as well as change the functional and structural components of lipoproteins. The triglyceride level is directly proportional to the severity of sepsis and associated with a systemic inflammatory response. The study aims to determine the correlation between the severity of bacterial sepsis with triglyceride value. An observational study with case control design from January2017 to March 2017 in 30 sepsis and 30 non-sepsis patients at H. Adam Malik General Hospital Medan. We examined Procalcitonin (PCT) and triglyceride level on the 1st, 3rd and 5th day and then analyzed using MannWhitney to assess their correlation.The triglyceride value in the sepsis group was 120 ± 5.1 mg/dl on day 1, non-sepsis 117.53 ± 36.37mg/dl. However, on the fifth day, the sepsis group of triglyceride values was 124.2±50.29mg/dl and the non-sepsis group triglyceride values 134.03±68.12mg/dl. There was no specific connection between the severity of sepsis and triglyceride value in a patient with sepsis.

  6. 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.

  7. 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

  8. Experience with polyclonal immunoglobulin therapy in poly trauma patients with severe sepsis

    International Nuclear Information System (INIS)

    Janjua, S.K.; Hussain, R.M.; Mohsin, S.T.; Iqbal, A.; Mishwani, A.H.

    2011-01-01

    To evaluate the effects of intravenous immunoglobulin therapy on progression of severe sepsis in patients of poly trauma. Design: Quasi-experimental study. Place and Duration of Study: Combined Military Hospital Peshawar from June 2008 to Dec 2009. Patients and Methods: Forty six patients of poly trauma with severe sepsis were included. Along with the standard management i.e., surgical management, fluid resuscitation, antibiotics, analgesics, ionotropic, ventilatory and nutritional support, IVIG 5% (intravenous immunoglobulin) was infused over a period of 6 hours and repeated for three consecutive days. Sequential Organ Failure Assessment (SOFA) score was used to assess the progress in all the patients. Results: At the time of enrolment mean SOFA score was 5.41+- 1.127 and on the 15 day it was 1.62 +- 2.24, mean age was 39.21+10.26 years. Thirty four patients (73.91%) developed gram negative sepsis and eighteen patients (39.13%) developed septic shock. Mean duration of stay in ICU and on ventilatory support was 20.80+9.61 and 10.52 + 5.52 days respectively. Thirty five days mortality rate of these patients was 30.43%. Conclusion: The IVIG administration, when used along with the standard management appears to improve significantly the prognosis in patients of poly trauma with severe sepsis. (author)

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

    Directory of Open Access Journals (Sweden)

    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

  10. [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.

  11. Biomarkers for sepsis: past, present and future

    Directory of Open Access Journals (Sweden)

    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.

  12. Sepsis and multiorgan failure following TVT procedure.

    Science.gov (United States)

    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.

  13. Sepsis - tunnistaminen ja hoito ensi- ja akuuttihoidossa

    OpenAIRE

    Ansio, Susa; Saarenketo, Tiia

    2016-01-01

    Sepsiksellä tarkoitetaan tilannetta, jolloin ihmisen verenkierrossa on bakteereita ja tämä aiheuttaa vakavia oireita. Lähes kaikki sepsiksen oireet johtuvat elimistön puolustusreaktiosta bakteeria vastaan. Sepsiksen hoito on monivaiheista ja kallista, ja siihen kuolleisuus on suurta. Ensihoidossa olisi tärkeää tunnistaa mahdollinen sepsis ja aloittaa tarvittava hoito mahdollisimman varhaisessa vaiheessa. Opinnäytetyön tarkoituksena on kuvata sepsiksen tunnistamista ensihoidossa, myöhäisem...

  14. In vitro diagnosis of sepsis: a review

    Directory of Open Access Journals (Sweden)

    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

  15. Development of Immunopathobiogenesis on SIRS-Sepsis

    Directory of Open Access Journals (Sweden)

    A Guntur Hermawan

    2009-04-01

    Full Text Available Over the past decade, sepsis has been diagnosed according to consensus guidelines established in 1991 as an infection in addition to the symptoms of systemic inflammatory response syndrome (SIRS. In addition to the previous criteria, the 2001 conference added several new diagnostic criteria for sepsis. Of particular interest was the inclusion of the biomarkers procalcitonin (PCT and C-reactive protein (CRP, despite the overall conclusion that it was premature to use biomarkers for sepsis diagnosis. The primary recommendation of the panel was the implementation of the Predisposition, insult Infection, Response, and Organ dysfunction (PIRO.The immune system has traditionally been devided into innate and adaptive components, each of which has a different role and function in defending the host against infectious agents. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The superantigens are able to induce toxic shock syndrome and can sometimes cause multiple organ failure via adaptive immune system. The superantigenic activity of the bacterial exotoxins can be attributed to their ability to cross-link major histocompatibility complex class II molecules on antigen-presenting cells outside the peptide groove with T-cell receptors to form a trimolecular complex. This trimolecular interaction leads to uncontrolled release of a number of proinflammatory cytokines. Proinflammatory cytokines especially IFN-γ and TNF-α, the key cytokines causing toxic shock syndrome. KEYWORDS: sepsis, innate immunity, adaptive.

  16. [Sepsis with Staphylococcus aureus in immunocompromised patients].

    Science.gov (United States)

    Petrache, Simona Magdalena; Miftode, Egidia; Vâţă, A; Petrovici, Cristina Mirela; Dorneanu, Olivia; Luca, V

    2009-01-01

    The aim of our study was to analyze clinical and biological characteristics of immunocompromised patients with staphylococcal sepsis and to compare with the same data in non-immunocompromised patients. The diagnosis of sepsis was made based on Bone criteria. MiniAPI system ID 32 STAPH was used for identification and antibiotic susceptibility was assessed by ATB STAPH method and by E-test for oxacillin and vancomycin. Among the 147 patients with Staphylococcus aureus sepsis--66.67% had concomitant immunosuppressive conditions (diabetes mellitus, liver diseases, renal failure, corticotherapy, etc). We have found a significant correlation between the immunosuppressed status and MRSA (methicillin-resistant Staphylococcus aureus) involvement (p = 0.0018) and also, between this group of patients and treatment failure (p = 0.0012). Because of the high rate of MRSA involvement in systemic infections in the Eastern region of Romania first intention treatment of patients with staphylococcal infections and conditions of immunosuppression must include antibiotics effective against methicillin-resistant strains.

  17. Sepsis due to clostridium septicum: case report

    International Nuclear Information System (INIS)

    Foga, M.M.; McGinn, G.J.; Kroeker, M.A.; Guzman, R.

    2000-01-01

    Clostridium septicum is an unusual anaerobic, gram-positive, gas-producing bacillus, which has been identified as a cause of fulminant rapidly fatal infection in humans. Infection with C. septicum usually occurs in patients with cancer, patients receiving immunosuppressive chemotherapy, or patients with a nonmalignant hematological disorder such as hemolytic uremic syndrome. C. septicum infection most commonly involves the abdomen, and a recent review article has identified 164 cases in the medical literature describing the abdominal findings in this disease. Intracranial manifestation of C. septicum infection are less common and include meningitis, cerebritis, abscess formation and pneumocephalus. There have been only 12 documented cases in the English literature describing central nervous system lesions associated with C. septicum. We present a case report of a 56-year-old man in whom septicemia due to C. septicum developed as a complication of Crohn's disease. To our knowledge, there has never been a previous report of C. septicum sepsis related to underlying Crohn's disease. Our case is also remarkable in that an intracerebral gas collection developed at the site of a mycotic infarct related to C. septicum bacteremia, Intracranial, intraparenchymal gas formation related to anaerobic infection is extremely rare; to our knowledge, this radiological finding related to C. septicum sepsis has been described in only 1 previous case report in the medical literature. We also describe the intra-abdominal manifestations of C. septicum sepsis that occurred in this patient as well as the associated radiographic and pathologic findings. (author)

  18. MicroRNA's are novel biomarkers in sepsis

    DEFF Research Database (Denmark)

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

    2015-01-01

    Purpose: Sepsis is one of the leading causes of death after admission to the intensive care unit (ICU). The discovery of small non-coding microRNAs (miRs) and their correlation to sepsis has gained increasing interest. Our aim was to systematically review the literature examining the association ...... searching the computational target prediction databases. Conclusion: Various miRs are associated with sepsis, but no corresponding predictor genes were found....

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

    Directory of Open Access Journals (Sweden)

    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.

  20. SIGNALING MECHANISMS IN SEPSIS-INDUCED IMMUNE DYSFUNCTION

    OpenAIRE

    Hasan, Zirak

    2013-01-01

    Sepsis and subsequent organ failure remain the major cause of mortality in intensive care units in spite of significant research efforts. The lung is the most vulnerable organ affected by early hyper-inflammatory immune response in septic patients. On the other hand, the septic insult induces immune dysfunction in later phases of sepsis which in turn increases susceptibility to infections. The aim of this thesis was to investigate early and late inflammatory mechanisms in abdominal sepsis ind...

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

    Science.gov (United States)

    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

    2017-03-01

    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 members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. 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, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects 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.

  2. The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model for Sepsis.

    Science.gov (United States)

    Phillips, Gary S; Osborn, Tiffany M; Terry, Kathleen M; Gesten, Foster; Levy, Mitchell M; Lemeshow, Stanley

    2018-05-01

    In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. Retrospective evaluation of prospectively collected data. Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. None. Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult

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

    Science.gov (United States)

    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

    2017-03-01

    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 members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. 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, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects 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.

  4. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction.

    Science.gov (United States)

    Reis, Patricia A; Alexandre, Pedro C B; D'Avila, Joana C; Siqueira, Luciana D; Antunes, Barbara; Estato, Vanessa; Tibiriça, Eduardo V; Verdonk, Franck; Sharshar, Tarek; Chrétien, Fabrice; Castro-Faria-Neto, Hugo C; Bozza, Fernando A

    2017-02-01

    Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5-10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response

  5. [Value of sepsis single-disease manage system in predicting mortality in patients with sepsis].

    Science.gov (United States)

    Chen, J; Wang, L H; Ouyang, B; Chen, M Y; Wu, J F; Liu, Y J; Liu, Z M; Guan, X D

    2018-04-03

    Objective: To observe the effect of sepsis single-disease manage system on the improvement of sepsis treatment and the value in predicting mortality in patients with sepsis. Methods: A retrospective study was conducted. Patients with sepsis admitted to the Department of Surgical Intensive Care Unit of Sun Yat-Sen University First Affiliated Hospital from September 22, 2013 to May 5, 2015 were enrolled in this study. Sepsis single-disease manage system (Rui Xin clinical data manage system, China data, China) was used to monitor 25 clinical quality parameters, consisting of timeliness, normalization and outcome parameters. Based on whether these quality parameters could be completed or not, the clinical practice was evaluated by the system. The unachieved quality parameter was defined as suspicious parameters, and these suspicious parameters were used to predict mortality of patients with receiver operating characteristic curve (ROC). Results: A total of 1 220 patients with sepsis were enrolled, included 805 males and 415 females. The mean age was (59±17) years, and acute physiology and chronic health evaluation (APACHE Ⅱ) scores was 19±8. The area under ROC curve of total suspicious numbers for predicting 28-day mortality was 0.70; when the suspicious parameters number was more than 6, the sensitivity was 68.0% and the specificity was 61.0% for predicting 28-day mortality. In addition, the area under ROC curve of outcome suspicious number for predicting 28-day mortality was 0.89; when the suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 78.0% for predicting 28-day mortality. Moreover, the area under ROC curve of total suspicious number for predicting 90-day mortality was 0.73; when the total suspicious parameters number was more than 7, the sensitivity was 60.0% and the specificity was 74.0% for predicting 90-day mortality. Finally, the area under ROC curve of outcome suspicious numbers for predicting 90

  6. 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

  7. Endothelial Activation: The Ang/Tie Axis in Sepsis

    Directory of Open Access Journals (Sweden)

    Aleksandra Leligdowicz

    2018-04-01

    Full Text Available Sepsis, a dysregulated host response to infection that causes life-threatening organ dysfunction, is a highly heterogeneous syndrome with no specific treatment. Although sepsis can be caused by a wide variety of pathogenic organisms, endothelial dysfunction leading to vascular leak is a common mechanism of injury that contributes to the morbidity and mortality associated with the syndrome. Perturbations to the angiopoietin (Ang/Tie2 axis cause endothelial cell activation and contribute to the pathogenesis of sepsis. In this review, we summarize how the Ang/Tie2 pathway is implicated in sepsis and describe its prognostic as well as therapeutic utility in life-threatening infections.

  8. Sepsis Within 30 Days of Geriatric Hip Fracture Surgery.

    Science.gov (United States)

    Bohl, Daniel D; Iantorno, Stephanie E; Saltzman, Bryan M; Tetreault, Matthew W; Darrith, Brian; Della Valle, Craig J

    2017-10-01

    Sepsis after hip fracture typically develops from one of the 3 potential infectious sources: urinary tract infection (UTI), pneumonia, and surgical site infection (SSI). The purpose of this investigation is to determine (1) the proportion of cases of sepsis that arises from each of these potential infectious sources; (2) baseline risk factors for developing each of the potential infectious sources; and (3) baseline risk factors for developing sepsis. The National Surgical Quality Improvement Program database was searched for geriatric patients (aged >65 years) who underwent surgery for hip fracture during 2005-2013. Patients subsequently diagnosed with sepsis were categorized according to concomitant diagnosis with UTI, SSI, and/or pneumonia. Multivariate regression was used to test for associations while adjusting for baseline characteristics. Among the 466 patients who developed sepsis (2.4% of all patients), 157 (33.7%) also had a UTI, 135 (29.0%) also had pneumonia, and 36 (7.7%) also had SSI. The rate of sepsis was elevated in patients who developed UTI (13.0% vs 1.7%; P sepsis (21.0% vs 3.8%; P Sepsis occurs in about 1 in 40 patients after geriatric hip fracture surgery. Of these septic cases, 1 in 3 is associated with UTI, 1 in 3 with pneumonia, and 1 in 15 with SSI. The cause of sepsis is often unknown on clinical diagnosis, and this distribution of potential infectious sources allows clinicians for direct identification and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Viewpoint on the current status of researches on sepsis

    Directory of Open Access Journals (Sweden)

    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.

  10. Pediatric sepsis in the developing world: challenges in defining sepsis and issues in post-discharge mortality.

    Science.gov (United States)

    Wiens, Matthew O; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J Mark; Ndamira, Andrew; Larson, Charles P

    2012-01-01

    Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.

  11. 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

  12. A Multicenter Survey of House Staff Knowledge About Sepsis and the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock".

    Science.gov (United States)

    Watkins, Richard R; Haller, Nairmeen; Wayde, Melinda; Armitage, Keith B

    2017-01-01

    We aimed to assess the knowledge, attitudes, and perceptions of resident physicians regarding sepsis in general and the Surviving Sepsis Campaign Guidelines in particular. After institutional review board approval, we surveyed internal medicine (IM) and emergency medicine (EM) house staff from 3 separate institutions. House staff were notified of the survey via e-mail from their residency director or chief resident. The survey was Internet-based (using http://www.surveymonkey.com ), voluntary, and anonymous. The Surviving Sepsis Campaign Guidelines were used to develop the survey. The survey was open between December 2015 and April 2016. No incentives for participation were given. Reminder e-mails were sent approximately every 3 to 4 weeks to all eligible participants. Comparisons of responses were evaluated using the N-1 2-proportion test. A total of 133 responses were received. These included 84 from IM house staff, 27 from EM house staff, and 22 who selected "other." Eighty (101/126) percent reported managing at least 1 patient with sepsis in the preceding 30 days, 85% (97/114) rated their knowledge of the Surviving Sepsis Guidelines as "very familiar" or at least "somewhat familiar," and 84% (91/108) believed their training in the diagnosis and management of sepsis was "excellent" or at least "good." However, 43% (47/108) reported not receiving any feedback on their treatment of patients with sepsis in the last 30 days, while 24% (26/108) received feedback once. Both IM and EM house staff received comparable rates of feedback (62% vs 48%, respectively; P = .21). For the 3 questions that directly tested knowledge of the guidelines, the scores of the IM and EM house staff were similar. Notably, house staff on the Surviving Sepsis Campaign Guidelines is warranted, along with more consistent feedback regarding their diagnosis and management of sepsis.

  13. Severe sepsis secondary to emphysematous cystitis

    Directory of Open Access Journals (Sweden)

    M.M. Gargouri

    2015-03-01

    Full Text Available Emphysematous cystitis (EC is a rare, rapidly progressive infection characterized by gas formation within the bladder wall. Gas production is mainly due to fermentation of glucose or albumin by the pathogenic organisms. We present the case of a patient with EC who presented with severe sepsis of unknown origin. He was also found to have two vesical calculi and a horseshoe kidney. EC was diagnosed on ultrasonography which showed circumferential, acoustic shadowing around the bladder wall. Computed tomography (CT confirmed the diagnosis. Rapid healing could be achieved with appropriate antibiotics and bladder drainage. Endoscopic disintegration of the stones was performed three weeks later, and follow-up was uneventful.

  14. 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...... oxidative burst, increased concentration of cytokine, and accumulation of granulocytes in lung tissue. Plasmapheresis reduced the oxidative burst, and there was a tendency towards a reduced accumulation of granulocytes in the lung. CONCLUSION: Though plasmapheresis was initiated early after the endotoxin...

  15. Biomarkers of Endothelial Cell Activation in Early Sepsis

    DEFF Research Database (Denmark)

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

    2013-01-01

    and mortality in sepsis and that (ii) soluble fms-like tyrosine kinase 1 (sFlt-1) holds promise as a novel prognostic marker in sepsis. METHODS: This was a prospective, multicenter, observational study of a convenience sample of emergency department (ED) patients with a suspected infection presenting to one...

  16. 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 ...

  17. Diagnostic methods in sepsis: the need of speed

    Directory of Open Access Journals (Sweden)

    Fernando Rodrigues Coelho

    2012-08-01

    Full Text Available OBJECTIVE: Sepsis is a common condition encountered in hospital environments. There is no effective treatment for sepsis, and it remains an important cause of death at intensive care units. This study aimed to discuss some methods that are available in clinics, and tests that have been recently developed for the diagnosis of sepsis. METHODS: A systematic review was performed through the analysis of the following descriptors: sepsis, diagnostic methods, biological markers, and cytokines. RESULTS: The deleterious effects of sepsis are caused by an imbalance between the invasiveness of the pathogen and the ability of the host to mount an effective immune response. Consequently, the host's immune surveillance fails to eliminate the pathogen, allowing it to spread. Moreover, there is a pro-inflammatory mediator release, inappropriate activation of the coagulation and complement cascades, leading to dysfunction of multiple organs and systems. The difficulty achieve total recovery of the patient is explainable. There is an increased incidence of sepsis worldwide due to factors such as aging population, larger number of surgeries, and number of microorganisms resistant to existing antibiotics. CONCLUSION: The search for new diagnostic markers associated with increased risk of sepsis development and molecules that can be correlated to certain steps of sepsis is becoming necessary. This would allow for earlier diagnosis, facilitate patient prognosis characterization, and prediction of possible evolution of each case. All other markers are regrettably constrained to research units.

  18. 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 ...

  19. 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 ...

  20. Seasonal Variation in the Emergency Department Prevalence Of Sepsis

    LENUS (Irish Health Repository)

    McNevin, C

    2018-05-01

    The incidence and mortality of sepsis and severe sepsis in hospitalised patients is seasonal and consistently highest during the winter. The primary aim of this study was to measure the seasonal variation in the prevalence of emergency department (ED) patients with sepsis. This cross-sectional study was performed over two four-week periods in the summer and in the winter, respectively. The clinical records of all patients presenting to the ED during the study periods were retrospectively screened to determine if they met the criteria for “uncomplicated” sepsis and severe sepsis or septic shock. The prevalence of “uncomplicated” sepsis was higher in the winter (43.9 per 1000) compared to the summer (30.7 per 1000). The prevalence of severe sepsis or septic shock was also higher in the winter (17.7 per 1000) compared to the summer (11.7 per 1000). This quantitatively demonstrates the increased ED burden of sepsis in the winter that can be used to inform healthcare planning and resource allocation.

  1. 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...

  2. 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.

  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. An unusual case of sepsis and petechial rash.

    Science.gov (United States)

    Gardner, Christina

    2017-05-01

    This article describes a man who presented to the ED in acute distress with signs and symptoms of sepsis, pneumonia, and a new petechial rash on his chest. He was eventually diagnosed with Rocky Mountain spotted fever. Aggressive treatment of sepsis and timely administration of empiric antibiotics were lifesaving in this situation.

  5. Inadequate exercise as a risk factor for sepsis mortality.

    Science.gov (United States)

    Williams, Paul T

    2013-01-01

    Test whether inadequate exercise is related to sepsis mortality. Mortality surveillance of an epidemiological cohort of 155,484 National Walkers' and Runners' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded. Sepsis was the underlying cause in 54 deaths (sepsis(underlying)) and a contributing cause in 184 deaths (sepsis(contributing)), or 238 total sepsis-related deaths (sepsis(total)). Inadequate exercise was associated with 2.24-fold increased risk for sepsis(underlying) (95%CI: 1.21 to 4.07-fold, P = 0.01), 2.11-fold increased risk for sepsis(contributing) (95%CI: 1.51- to 2.92-fold, P<10(-4)), and 2.13-fold increased risk for sepsis(total) (95%CI: 1.59- to 2.84-fold, P<10(-6)) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsis(total) risk was greater in diabetics (P = 10(-5)), cancer survivors (P = 0.0001), and heart attack survivors (P = 0.003) and increased with waist circumference (P = 0.0004). The sepsis(total) risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsis(total) risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P = 0.0001) when adjusted, which was significantly greater (P = 0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P = 0

  6. 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

  7. Plasma procalcitonin concentrations are increased in dogs with sepsis

    Science.gov (United States)

    Goggs, Robert; Milloway, Matthew; Troia, Roberta; Giunti, Massimo

    2018-01-01

    Sepsis, the life-threatening organ dysfunction caused by a dysregulated host response to infection, is difficult to identify and to prognosticate for. In people with sepsis, procalcitonin (PCT) measurement aids diagnosis, enables therapeutic monitoring and improves prognostic accuracy. This study used a commercial canine PCT assay to measure plasma PCT concentrations in dogs with gastric dilatation volvulus (GDV) syndrome and in dogs with sepsis. It was hypothesised that dogs with GDV syndrome and with sepsis have greater plasma PCT concentrations than healthy dogs and that dogs with sepsis have greater PCT concentrations than dogs with GDV syndrome. Before analysing canine plasma samples, the ability of the assay to identify canine PCT, in addition to assay imprecision and the lower limit of detection were established. The assay had low imprecision with coefficients of variation ≤4.5 per cent. The lower limit of detection was 3.4 pg/ml. Plasma PCT concentrations were measured in 20 dogs with sepsis, in 32 dogs with GDV syndrome and in 52 healthy dogs. Median (IQR) PCT concentration in dogs with sepsis 78.7 pg/ml (39.1–164.7) was significantly greater than in healthy dogs 49.8 pg/ml (36.2–63.7) (P=0.019), but there were no significant differences between PCT concentrations in dogs with GDV syndrome and controls (P=0.072) or between dogs with sepsis and GDV syndrome (P=1.000). Dogs with sepsis have significantly increased plasma PCT concentrations compared with healthy dogs, although considerable overlap between these populations was identified. Future investigations should confirm this finding in other populations and evaluate the diagnostic and prognostic value of PCT in dogs with sepsis. PMID:29682292

  8. 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.

  9. Sepsis and cytomegalovirus: foes or conspirators?

    Science.gov (United States)

    Mansfield, Sara; Grießl, Marion; Gutknecht, Michael; Cook, Charles H

    2015-06-01

    Cytomegalovirus (CMV) reactivation in non-immune-suppressed critically ill patients is an area of increasing interest. CMV has long been appreciated as a pathogen in immunocompromised hosts. CMV reactivates in approximately one-third of latently infected non-immune-suppressed hosts during critical illness; however, its role as a pathogen in these patients remains unclear. CMV reactivation has been linked to bacterial sepsis and likely results from inflammation, transient immune compromise, and viral epigenetic changes. While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts. These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis. While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed. Here we review the current literature and highlight areas for future investigation.

  10. Avances en el desarrollo de terapias neutralizantes en la sepsis Advances in the development of neutralizing therapies for sepsis

    Directory of Open Access Journals (Sweden)

    Maria Florencia Henning

    2006-06-01

    beneficial for the host. However, if the amount of LPS released exceeds the critical concentration threshold an augmented release of inflammatory cytokines as TNF-a, and interleukines (IL produce a severe sepsis. This fact led us to find therapeutical alternatives able to neutralize circulating endotoxin. This work is focused on the experimental results obtained in vivo and in vitro using synthetic proteins and peptides in order to neutralize LPS, and on future perpectives in this research area that offer the use of lipoprotein and in particular apolipoprotein A-I and mutants or peptides derived from this protein.

  11. Sepsis and Shock Response Team: Impact of a Multidisciplinary Approach to Implementing Surviving Sepsis Campaign Guidelines and Surviving the Process.

    Science.gov (United States)

    Grek, Ami; Booth, Sandra; Festic, Emir; Maniaci, Michael; Shirazi, Ehsan; Thompson, Kristine; Starbuck, Angela; Mcree, Chad; Naessens, James M; Moreno Franco, Pablo

    The Surviving Sepsis Campaign guidelines are designed to decrease mortality through consistent application of a 7-element bundle. This study evaluated the impact of improvement in bundle adherence using a time-series analysis of compliance with the bundle elements before and after interventions intended to improve the process, while also looking at hospital mortality. This article describes interventions used to improve bundle compliance and hospital mortality in patients admitted through the emergency department with sepsis, severe sepsis, or septic shock. Quality improvement methodology was used to develop high-impact interventions that led to dramatically improved adherence to the Surviving Sepsis Campaign guidelines bundle. Improved performance was associated with a significant decrease in the in-hospital mortality of severe sepsis patients presenting to the emergency department.

  12. 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

  13. 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.

  14. Personalized identification of differentially expressed pathways in pediatric sepsis.

    Science.gov (United States)

    Li, Binjie; Zeng, Qiyi

    2017-10-01

    Sepsis is a leading killer of children worldwide with numerous differentially expressed genes reported to be associated with sepsis. Identifying core pathways in an individual is important for understanding septic mechanisms and for the future application of custom therapeutic decisions. Samples used in the study were from a control group (n=18) and pediatric sepsis group (n=52). Based on Kauffman's attractor theory, differentially expressed pathways associated with pediatric sepsis were detected as attractors. When the distribution results of attractors are consistent with the distribution of total data assessed using support vector machine, the individualized pathway aberrance score (iPAS) was calculated to distinguish differences. Through attractor and Kyoto Encyclopedia of Genes and Genomes functional analysis, 277 enriched pathways were identified as attractors. There were 81 pathways with Ppathways with Ppathway clusters and four sample clusters. Thus, in the majority pediatric sepsis samples, core pathways can be detected as different from accumulated normal samples. In conclusion, a novel procedure that identified the dysregulated attractors in individuals with pediatric sepsis was constructed. Attractors can be markers to identify pathways involved in pediatric sepsis. iPAS may provide a correlation score for each of the signaling pathways present in an individual patient. This process may improve the personalized interpretation of disease mechanisms and may be useful in the forthcoming era of personalized medicine.

  15. 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...... of disease history to scoring based on within-admission clinical measurements emphasizing the value of long term data in novel patient scores that combine the two types of data.......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 history...... recurrent trajectories of time-ordered co-morbidities had significantly increased sepsis mortality compared to those who did not follow a trajectory. We identified trajectories which significantly altered sepsis mortality, and found three major starting points in a combined temporal sepsis network: Alcohol...

  16. 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?

  17. Early onset neonatal sepsis in preterm premature rupture of membranes

    International Nuclear Information System (INIS)

    Ashraf, M.N.

    2015-01-01

    To determine the frequency of early onset neonatal sepsis in newborn with various duration of preterm premature rupture of membranes (PPROM). Study Design: Cross sectional study. Place and Duration of Study: Neonatal Intensive Care Unit Combined Military Hospital, Lahore from November 2009 to November 2010. Material and Methods: Neonates of singleton pregnancies complicated by preterm premature rupture of the membranes (PPROM) with delivery between 30 and 36 weeks gestation were included in the study. The overall frequency of neonatal sepsis was calculated on clinical and serological basis. Comparison of the frequency of sepsis among groups with varying duration of rupture of membranes was done. Results: Out of 164 babies, 84 (51.2%) were female and 80 (48.8%) were male. Mean maternal age was 23 years (range: 18-36 years). Mean gestational age was 33 weeks (range: 30-36 weeks). Sepsis was suspected in 41(25%) babies on clinical grounds. C-reactive protein was raised in 36 (22%) neonates. There was statistically insignificant difference between clinical versus serological diagnosis (p=0.515). Frequency of neonatal sepsis was significantly higher in mothers with longer duration of rupture of membrane (p < 0.001). Conclusion: Frequency of neonatal sepsis was observed to be 22%. PPROM is an important risk factor for early onset neonatal sepsis. (author)

  18. Neonatal sepsis: Highlighting the principles of diagnosis and management

    Directory of Open Access Journals (Sweden)

    Melantha Coetzee

    2017-07-01

    Full Text Available 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 sepsis to be 8.5 - 10%, with late-onset sepsis accounting for most of these infections. The diagnosis of neonatal sepsis is not always straightforward, and the initiation and continuation of antimicrobials in these situations relies on good clinical judgment. The need for empirical antimicrobials is driven by the existence of risk factors for early-onset sepsis and clinical symptoms and signs of late-onset sepsis. Antimicrobial stewardship programmes should be in place to guide clinicians to either stop, change, or continue antimicrobials. Institution-specific knowledge of the most common pathogens and the antimicrobial susceptibility pattern is important to prevent the emergence of further antimicrobial resistance.

  19. 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.

  20. Serum amyloid A in the diagnosis of feline sepsis.

    Science.gov (United States)

    Troìa, Roberta; Gruarin, Marta; Foglia, Armando; Agnoli, Chiara; Dondi, Francesco; Giunti, Massimo

    2017-11-01

    Systemic inflammatory response syndrome (SIRS) and sepsis can be challenging to diagnose in cats. Retrospectively, we investigated the diagnostic and prognostic potential of serum amyloid A (SAA), a major feline acute-phase protein (APP), in a population of critically ill cats with SIRS related to trauma or sepsis. A total of 56 SIRS cats (trauma n = 27; sepsis n = 29) were included and compared with healthy controls ( n = 18). SAA concentration was significantly increased in SIRS cats compared to controls, confirming its potential for the detection of systemic inflammation in this species. Significantly higher values of SAA were detected in cats belonging to the sepsis group; however, according to the results of the receiver operating characteristic curve analysis, the value of using SAA (>81 mg/L) to discriminate septic cats was only moderate (AUC = 0.76). Additionally, cats with sepsis had significantly higher serum bilirubin concentrations and toxic neutrophil changes compared to the trauma group. Overall, 38 of 56 cats were survivors; 18 of 56 were non-survivors, with 83% of the non-survivors (15 of 18) belonging to the sepsis group. Serum bilirubin concentration, but not SAA, was able to predict outcome. Prospective studies are needed to assess the potential of SAA in the diagnosis of feline sepsis and outcome prediction.

  1. [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.

  2. Biomarkers, Trauma, and Sepsis in Pediatrics: A Review

    Directory of Open Access Journals (Sweden)

    Marianne Frieri

    2016-01-01

    Full Text Available Context: There is a logical connection with biomarkers, trauma, and sepsis. This review paper provides new information and clinical practice implications. Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Stress management both in trauma is based upon the notion that stress causes an immune imbalance in susceptible individuals. Evidence Acquisition: Data sources included studies indexed in PubMed, a meta- analysis, predictive values, research strategies, and quality assessments. A recent paper by one of the authors stated marked increase in serum procalcitonin during the course of a septic process often indicates an exacerbation of the illness, and a decreasing level is a sign of improvement. A review of epidemiologic studies on pediatric soccer patients was also addressed. Keywords for searching included biomarkers, immunity, trauma, and sepsis. Results: Of 50 reviewed articles, 34 eligible articles were selected including biomarkers, predictive values for procalcitonin, identifying children at risk for intra-abdominal injuries, blunt trauma, and epidemiology, a meta-analysis. Of neonatal associated sepsis, the NF-kappa B pathway by inflammatory stimuli in human neutrophils, predictive value of gelsolin for the outcomes of preterm neonates, a meta-analysis interleukin-8 for neonatal sepsis diagnosis. Conclusions: Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms, and physiological functions of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Various topics were covered such as biomarkers, trauma, sepsis, inflammation, innate immunity, role of neutrophils and IL-8, reactive oxygen species

  3. 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.

  4. 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

  5. Sepsis from dropped clips at laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Hussain, Sarwat

    2001-01-01

    We report seven patients in whom five dropped surgical clips and two gallstones were visualized in the peritoneal cavity, on radiological studies. In two, subphrenic abscesses and empyemas developed as a result of dropped clips into the peritoneal cavity during or following laparoscopic cholecystectomy. In one of these two, a clip was removed surgically from the site of an abscess. In two other patients dropped gallstones, and in three, dropped clips led to no complications. These were seen incidentally on studies done for other indications. Abdominal abscess secondary to dropped gallstones is a well-recognized complication of laparoscopic cholecystectomy (LC). We conclude that even though dropped surgical clips usually do not cause problems, they should be considered as a risk additional to other well-known causes of post-LC abdominal sepsis

  6. Predictors of neonatal sepsis in developing countries.

    Science.gov (United States)

    Weber, Martin W; Carlin, John B; Gatchalian, Salvacion; Lehmann, Deborah; Muhe, Lulu; Mulholland, E Kim

    2003-08-01

    Neonatal infections are a major cause of death worldwide. Simple procedures for identifying infants with infection that need referral for treatment are therefore of major public health importance. We investigated 3303 infants Ethiopia, The Gambia, Papua New Guinea and The Philippines, using a standardized approach. Historical factors and clinical signs predicting sepsis, meningitis, hypoxemia, deaths and an ordinal scale indicating severe disease were investigated by logistic regression, and the performance of simple combination rules was explored. In multivariable analysis, reduced feeding ability, no spontaneous movement, temperature >38 degrees C, being drowsy/unconscious, a history of a feeding problem, history of change in activity, being agitated, the presence of lower chest wall indrawing, respiratory rate >60 breaths/min, grunting, cyanosis, a history of convulsions, a bulging fontanel and slow digital capillary refill were independent predictors of severe disease. The presence of any 1 of these 14 signs had a sensitivity for severe disease (defined as sepsis, meningitis, hypoxemia, or radiologically proven pneumonia) of 87% and a specificity of 54%. More stringent combinations, such as demanding 2 signs from the list, resulted in a considerable loss of sensitivity. By contrast only slight loss of sensitivity and considerable gain of specificity resulted from reducing the list to 9 signs. Requiring the presence of fever and any other sign produced a diagnostic rule with extremely low sensitivity (25%). Physical signs can be used to identify young infants at risk of severe disease, however with limited specificity, resulting in large numbers of unnecessary referrals. Further studies are required to validate and refine the prediction of severe disease, especially in the first week of life, but there appear to be limits on the accuracy of prediction that is achievable.

  7. Does Dexamethasone Helps in Meningococcal Sepsis?

    Science.gov (United States)

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

    2017-01-01

    Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:28974828

  8. In-111 WBC imaging in musculoskeletal sepsis

    International Nuclear Information System (INIS)

    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 μCi. 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

  9. Quantifying the improvement in sepsis diagnosis, documentation, and coding: the marginal causal effect of year of hospitalization on sepsis diagnosis.

    Science.gov (United States)

    Jafarzadeh, S Reza; Thomas, Benjamin S; Marschall, Jonas; Fraser, Victoria J; Gill, Jeff; Warren, David K

    2016-01-01

    To quantify the coinciding improvement in the clinical diagnosis of sepsis, its documentation in the electronic health records, and subsequent medical coding of sepsis for billing purposes in recent years. We examined 98,267 hospitalizations in 66,208 patients who met systemic inflammatory response syndrome criteria at a tertiary care center from 2008 to 2012. We used g-computation to estimate the causal effect of the year of hospitalization on receiving an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for sepsis by estimating changes in the probability of getting diagnosed and coded for sepsis during the study period. When adjusted for demographics, Charlson-Deyo comorbidity index, blood culture frequency per hospitalization, and intensive care unit admission, the causal risk difference for receiving a discharge code for sepsis per 100 hospitalizations with systemic inflammatory response syndrome, had the hospitalization occurred in 2012, was estimated to be 3.9% (95% confidence interval [CI], 3.8%-4.0%), 3.4% (95% CI, 3.3%-3.5%), 2.2% (95% CI, 2.1%-2.3%), and 0.9% (95% CI, 0.8%-1.1%) from 2008 to 2011, respectively. Patients with similar characteristics and risk factors had a higher of probability of getting diagnosed, documented, and coded for sepsis in 2012 than in previous years, which contributed to an apparent increase in sepsis incidence. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. 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.

  11. 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....

  12. 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...

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

    African Journals Online (AJOL)

    As sepsis progresses to septic shock, the risk of dying increases ... Jantjie Taljaard's current fields of interests are general internal medicine, antibiotic stewardship, HIV/HBV co-infection, drug-related .... infections (infection control) and stress.

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

    International Nuclear Information System (INIS)

    Barkhausen, J.; Stoeblen, F.; Mueller, R.D.

    1999-01-01

    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.)

  15. 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.)

  16. Metabolomics in Sepsis and Its Impact on Public Health.

    Science.gov (United States)

    Evangelatos, Nikolaos; Bauer, Pia; Reumann, Matthias; Satyamoorthy, Kapaettu; Lehrach, Hans; Brand, Angela

    2017-01-01

    Sepsis, with its often devastating consequences for patients and their families, remains a major public health concern that poses an increasing financial burden. Early resuscitation together with the elucidation of the biological pathways and pathophysiological mechanisms with the use of "-omics" technologies have started changing the clinical and research landscape in sepsis. Metabolomics (i.e., the study of the metabolome), an "-omics" technology further down in the "-omics" cascade between the genome and the phenome, could be particularly fruitful in sepsis research with the potential to alter the clinical practice. Apart from its benefit for the individual patient, metabolomics has an impact on public health that extends beyond its applications in medicine. In this review, we present recent developments in metabolomics research in sepsis, with a focus on pneumonia, and we discuss the impact of metabolomics on public health, with a focus on free/libre open source software. © 2018 S. Karger AG, Basel.

  17. [New Concept for Surviving Sepsis: from Phenomenon to Essence].

    Science.gov (United States)

    Liao, Xue-Lian; Xie, Zhi-Chao; Kang, Yan

    2016-07-01

    Sepsis is a critical clinical syndrome which keep puzzling the medical profession for many years. Recently, the results from several large-scale trials challenged the necessity of early goal directed therapy (EGDT) in surviving sepsis bundle, These trials were not opposed to EGDT but bring new concept that it is essential to utilize therapy with multiple monitoring measures in order to minimize injury while guarantee the safety . Deeper understanding in the pathogenesis of sepsis gives rise to the update of its definition based on vital organ dysfunction. The importance of dynamic monitoring in defining sepsis also need to be emphasized. Developing more effective monitoring measures could provide better treatments, thus improve the prognosis of septic patients. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

  18. 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,

  19. 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.

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

    African Journals Online (AJOL)

    count has a poor positive predictive value for neonatal sepsis and is ... Division of Neonatology, Department of Paediatrics and Child Health, School of Medicine, University ... infections (UTIs) in neonates,[18] many clinicians use the following.

  1. Renal blood flow in sepsis: a complex issue

    OpenAIRE

    Molitoris, Bruce A

    2005-01-01

    The clinical complexity of sepsis and the regional variability in renal blood flow present a difficult challenge for the clinician or investigator in understanding the role and clinical importance of reduced blood flow in the pathophysiology of sepsis-induced acute renal failure. Understanding the role of regional microvasculature flow and interactions between endothelium and white blood cells in the local delivery of oxygen and substrates is of critical importance. Therefore, measuring total...

  2. A Complex Systems View of Sepsis: Implications for Nursing

    Science.gov (United States)

    2013-02-01

    multi- faceted approach to the management of sepsis. Rapid pro- vision of broad-spectrum antibiotic coverage is coupled with aggressive organ support...setting of sepsis may include (1) exposure to infectious agents, (2) immunocompromise , (3) injury or illness, (4) genetic abnormalities, or (5) under- lying...assays 2. Obtain culture panel (blood, respiratory, urine, wound) 3. Prompt administration of broad-spectrum antibiotics 4. Manage organ dysfunction

  3. 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.

  4. 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) sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated 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.

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

    Science.gov (United States)

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

    2013-02-01

    To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B

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

    Science.gov (United States)

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

    2013-02-01

    To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de

  7. Spontaneous neutrophil migration patterns during sepsis after major burns.

    Science.gov (United States)

    Jones, Caroline N; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A; Warren, H Shaw; Tompkins, Ronald G; Fagan, Shawn P; Irimia, Daniel

    2014-01-01

    Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns.

  8. Sepsis after renal transplantation: Clinical, immunological, and microbiological risk factors.

    Science.gov (United States)

    Schachtner, Thomas; Stein, Maik; Reinke, Petra

    2017-06-01

    As immunosuppressive therapy and allograft survival have improved, the increased incidence of sepsis has become a major hurdle of disease-free survival after renal transplantation. We identified 112 of 957 kidney transplant recipients (KTRs) with sepsis. In all, 31 KTRs developed severe sepsis or septic shock, and 30 KTRs died from sepsis. KTRs without sepsis were used for comparison. CMV-specific and alloreactive T cells were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified by lymphocyte subpopulations. Five-year patient survival was 70.3% with sepsis compared to 88.2% without (Psepsis (Psepsis (Psepsis was associated with decreased CD3+ and CD4+ T cells pre-transplantation (Psepsis (Psepsis (Psepsis show inferior patient survival and allograft function. Identified risk factors and differences in lymphocyte counts, CMV-specific immunity, and alloreactivity may prove useful to identify KTRs at increased risk. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Role of Circulating Lymphocytes in Patients with Sepsis

    Directory of Open Access Journals (Sweden)

    Raul de Pablo

    2014-01-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Schotter, Joerg; Shoshi, Astrit; Brueckl, Hubert

    2009-01-01

    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. A patient cohort on long-term sequelae of sepsis survivors: study protocol of the Mid-German Sepsis Cohort.

    Science.gov (United States)

    Scherag, André; Hartog, Christiane S; Fleischmann, Carolin; Ouart, Dominique; Hoffmann, Franziska; König, Christian; Kesselmeier, Miriam; Fiedler, Sandra; Philipp, Monique; Braune, Anke; Eichhorn, Cornelia; Gampe, Christin; Romeike, Heike; Reinhart, Konrad

    2017-08-23

    An increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors. All patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally. The study is conducted according to the current version of the Declaration of Helsinki and has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals. German Clinical Trials Registry DRKS00010050. © 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.

  13. 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

  14. 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

    Directory of Open Access Journals (Sweden)

    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

  15. 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.

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

    Science.gov (United States)

    Chacko, Cyril Jacob; Gopal, Shameer

    2015-01-01

    We proposed a review of present literature and systematic analysis of present literature to summarize the evidence on the use of β-blockers on the outcome of a patient with severe sepsis and septic shock. Medline, EMBASE, Cochrane Library were searched from 1946 to December 2013. The bibliography of all relevant articles was hand searched. Full-text search of the grey literature was done through the medical institution database. The database search identified a total of 1241 possible studies. The citation list was hand searched by both the authors. A total of 9 studies were identified. Most studies found a benefit from β-blocker administration in sepsis. This included improved heart rate (HR) control, decreased mortality and improvement in acid-base parameters. Chronic β-blocker usage in sepsis was also associated with improved mortality. The administration of β-blockers during sepsis was associated with better control of HR. The methodological quality of all the included studies, however, was poor. 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.

  17. Pediatric sepsis in the developing world: challenges in defining sepsis and issues in post-discharge mortality

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    Larson CP

    2012-11-01

    Full Text Available Matthew O Wiens,1 Elias Kumbakumba,2 Niranjan Kissoon,3 J Mark Ansermino,4 Andrew Ndamira,2 Charles P Larson51School of Population and Public Health, University of British Columbia, Vancouver, Canada; 2Department of Pediatrics, Mbarara University of Science and Technology, Mbarara, Uganda; 3Department of Pediatrics, BC Children's Hospital and University of British Columbia, Vancouver, Canada; 4Department of Anesthesia, BC Children's Hospital and University of British Columbia, Vancouver, Canada; 5Department of Pediatrics and School of Population and Public Health, University of British Columbia, Vancouver, CanadaAbstract: Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.Keywords: children, pediatric sepsis, developing countries

  18. Pregnancy-Associated Severe Sepsis: Contemporary State and Future Challenges.

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    Oud, Lavi

    2014-12-01

    Pregnancy is associated with an increased risk of infection related to its associated mechanical and physiological changes. Sepsis remains among the top causes of maternal death worldwide and is associated with substantial maternal morbidity. However, there are sparse data on pregnancy-associated severe sepsis (PASS), related in part to infrequent reports, varying case definitions and methodological approach, small cohort size, and often limited focus on severe sepsis in selected phases of pregnancy outcomes. Available reports vary, but indicate that PASS is a rare but likely increasing complication, and it is more likely to develop with increased maternal age, among minority women, the poor, those lacking health insurance, those with chronic illness or pregnancy-associated complications, and following invasive procedures. Obstetric sites of infection are the most prevalent, but non-obstetric infections often underlie pregnancy-associated severe sepsis, though the source of infection is often not readily apparent during initial care. Women with PASS can have a rapidly fatal course and require heightened clinician vigilance for early diagnosis and timely effective intervention. Nevertheless, available reports raise concerns about prevalent substandard care of these patients, contributing to adverse outcomes. The case fatality of PASS appears lower than that in the general population with severe sepsis, while the long-term outcomes of survivors remain unknown.

  19. The Microcirculation System in Critical Conditions Caused by Abdominal Sepsis

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    S. L. Kan

    2011-01-01

    Full Text Available Objective: to evaluate the microcirculation system in critical conditions caused by abdominal sepsis for a further differentiated approach to intensive care. Subjects and methods. Twenty-four patients with abdominal sepsis (mean age 42.9±0.9 years were examined; a control group consisted of 35 apparently healthy individuals (mean age 40.1±2.1 years. Over 11 days, the microcirculatory bed was evaluated by cutaneous laser Doppler flowmetry by means of a ЛАКК-02 laser capillary blood flow analyzer made in the Russian Federation (LAZMA Research-and-Production Association, by using a basic light guide for percutaneous microcirculation studies. Results. Throughout the study, tissue blood perfusion remained in the patients with sepsis due to the higher effect of mainly active components of vascular tone regulation on the microvascular bed. In a poor outcome, there was a reduction in both active and passive regulatory effects on tissue perfusion chiefly due to local (myogenic factors. Conclusion. The findings suggest that the patients with sepsis have microcirculatory regulation changes aimed at maintaining tissue perfusion. A follow-up of the microcirculation may be useful in choosing intensive care tactics and predicting disease outcome. Key words: sepsis, microcirculation, microvascular bed, micro blood flow, tissue perfusion.

  20. Sepsis and ARDS: The Dark Side of Histones

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    Xu, Zhiheng; Huang, Yongbo; Mao, Pu; Zhang, Jianrong; Li, Yimin

    2015-01-01

    Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases. PMID:26609197

  1. Significance of blood pressure variability in patients with sepsis.

    Science.gov (United States)

    Pandey, Nishant Raj; Bian, Yu-Yao; Shou, Song-Tao

    2014-01-01

    This study was undertaken to observe the characteristics of blood pressure variability (BPV) and sepsis and to investigate changes in blood pressure and its value on the severity of illness in patients with sepsis. Blood parameters, APACHE II score, and 24-hour ambulatory BP were analyzed in 89 patients with sepsis. In patients with APACHE II score>19, the values of systolic blood pressure (SBPV), diasystolic blood pressure (DBPV), non-dipper percentage, cortisol (COR), lactate (LAC), platelet count (PLT) and glucose (GLU) were significantly higher than in those with APACHE II score ≤19 (Pblood cell (WBC), creatinine (Cr), PaO2, C-reactive protein (CRP), adrenocorticotropic hormone (ACTH) and tumor necrosis factor α (TNF-α) were not statistically significant (P>0.05). Correlation analysis showed that APACHE II scores correlated significantly with SBPV and DBPV (P0.05). Logistic regression analysis of SBPV, DBPV, APACHE II score, and LAC was used to predict prognosis in terms of survival and non-survival rates. Receiver operating characteristics curve (ROC) showed that DBPV was a better predictor of survival rate with an AUC value of 0.890. However, AUC of SBPV, APACHE II score, and LAC was 0.746, 0.831 and 0.915, respectively. The values of SBPV, DBPV and non-dipper percentage are higher in patients with sepsis. DBPV and SBPV can be used to predict the survival rate of patients with sepsis.

  2. 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.

  3. Profil Sepsis Neonatus di Unit Perawatan Neonatus RSUP H Adam Malik Medan Tahun 2008 - 2010

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    Pertin Sianturi

    2016-11-01

    Kesimpulan. Sepsis salah satu penyebab utama kematian neonatus yang dipengaruhi oleh berat lahir rendah, prematuritas, resistensi kuman terhadap antibiotik empirik dan jenis kuman. Penyebab sepsis neonatus terbanyak adalah kuman Gram negatif yang berkontribusi terhadap angka mortalitas

  4. Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

    Science.gov (United States)

    Vallabhajosyula, S; Pruthi, S; Shah, S; Wiley, B M; Mankad, S V; Jentzer, J C

    2018-01-01

    Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

  5. 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

  6. Accurate coding in sepsis: clinical significance and financial implications.

    Science.gov (United States)

    Chin, Y T; Scattergood, N; Thornber, M; Thomas, S

    2016-09-01

    Sepsis is a major healthcare problem and leading cause of death worldwide. UK hospital mortality statistics and payments for patient episodes of care are calculated on clinical coding data. The accuracy of these data depends on the quality of coding. This study aimed to investigate whether patients with significant bacteraemia are coded for sepsis and to estimate the financial costs of miscoding. Of 54 patients over a one-month period with a significant bacteraemia, only 19% had been coded for sepsis. This is likely to lead to falsely high calculated hospital mortality. Furthermore, this resulted in an underpayment of £21,000 for one month alone. Copyright © 2016 The Healthcare Infection Society. All rights reserved.

  7. The coagulopathy in sepsis: significance and implications for treatment

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    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.

  8. Intracranial Pressure during HighVolume Hemofiltration in Severe Sepsis

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    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.

  9. The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.

    Science.gov (United States)

    Rayes, Julie; Lax, Siân; Wichaiyo, Surasak; Watson, Stephanie K; Di, Ying; Lombard, Stephanie; Grygielska, Beata; Smith, Stuart W; Skordilis, Kassiani; Watson, Steve P

    2017-12-21

    Platelets play a critical role in vascular inflammation through the podoplanin and collagen/fibrin receptors, C-type-lectin-like-2 (CLEC-2) and glycoprotein VI (GPVI), respectively. Both receptors regulate endothelial permeability and prevent peri-vascular bleeding in inflammation. Here we show that platelet-specific deletion of CLEC-2 but not GPVI leads to enhanced systemic inflammation and accelerated organ injury in two mouse models of sepsis-intra-peritoneal lipopolysaccharide and cecal ligation and puncture. CLEC-2 deficiency is associated with reduced numbers of podoplanin-expressing macrophages despite increased cytokine and chemokine levels in the infected peritoneum. Pharmacological inhibition of the interaction between CLEC-2 and podoplanin regulates immune cell infiltration and the inflammatory reaction during sepsis, suggesting that activation of podoplanin underlies the anti-inflammatory action of platelet CLEC-2. We suggest podoplanin-CLEC-2 as a novel anti-inflammatory axis regulating immune cell recruitment and activation in sepsis.

  10. Immature platelet fraction in bacterial sepsis severity assessment

    Science.gov (United States)

    Djuang, M. H.; Ginting, F.; Hariman, H.

    2018-03-01

    Sepsis is an infection-induced syndrome, mostly caused by bacteria, of organ dysfunctions that caused by host response dysregulations. One of the simplest sepsis-indicator is platelet and its indexes. A new platelet parameter called immature platelet count (IPF) became theinterest in this study. The study aims to see whether IPF could assess sepsis severity by procalcitonin (PCT).Sixty-four of seventy-one patients with increased PCT were included in this cross-sectional study and separated into three groups based on their PCT levels. IPF showed no significance among the three groups (p-value>0.05) while platelet count was significant (p-valuesepsis severity based on PCT showed larger platelet count, as the result of platelet destructions caused by pro-inflammatory cytokines and endotoxins.

  11. Sepsis patients' renal manifestation on contrast-enhanced CT

    International Nuclear Information System (INIS)

    Sasaguri, K.; Yamaguchi, K.; Nakazono, T.; Mizuguchi, M.; Irie, H.

    2016-01-01

    Aim: To evaluate renal volume and attenuation changes in patients with sepsis on contrast-enhanced computed tomography (CT) with respect to the severity of sepsis. Materials and methods: Forty-four patients with sepsis who underwent CT before and after the onset of sepsis were retrospectively analysed. Renal volume and CT attenuation value of the renal cortex on contrast-enhanced CT were measured for each patient and changes in renal volume and CT attenuation value from before to after the onset of sepsis were calculated. The changes were correlated with the severity of sepsis (Sepsis-related Organ Failure Assessment [SOFA] score). The time course of the renal volume and CT attenuation changes were also evaluated. Results: Renal volume increased by 17.6% and CT attenuation value decreased by 19% after the onset of sepsis with statistically significant differences (p<0.001 for both renal volume and CT attenuation changes). The renal volume and CT attenuation changes had significant correlations with the SOFA score (r=0.36, p=0.018 and −0.43, p=0.005, respectively). The time course of the renal volume and CT attenuation changes seemed to be gradual compared to that of the SOFA score and to lag behind the peak of the SOFA score. Conclusion: In patients with sepsis, the renal volume increases and the CT attenuation value decreases in proportion to the severity of sepsis. The changes may lag behind the peak of severity of sepsis and can be observed for a relatively long time after a patient's recovery from sepsis. - Highlights: • The renal volume increases and the renal enhancement on contrast-enhanced CT decreases in patients with sepsis. • The degrees of these changes are correlated with severity of sepsis. • These changes may lag behind the peak of severity of sepsis and last for a long time after a patient's recovery from sepsis.

  12. An Interpretable Machine Learning Model for Accurate Prediction of Sepsis in the ICU.

    Science.gov (United States)

    Nemati, Shamim; Holder, Andre; Razmi, Fereshteh; Stanley, Matthew D; Clifford, Gari D; Buchman, Timothy G

    2018-04-01

    Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis. Observational cohort study. Academic medical center from January 2013 to December 2015. Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively. None. High-resolution vital signs time series and electronic medical record data were extracted. A set of 65 features (variables) were calculated on hourly basis and passed to the Artificial Intelligence Sepsis Expert algorithm to predict onset of sepsis in the proceeding T hours (where T = 12, 8, 6, or 4). Artificial Intelligence Sepsis Expert was used to predict onset of sepsis in the proceeding T hours and to produce a list of the most significant contributing factors. For the 12-, 8-, 6-, and 4-hour ahead prediction of sepsis, Artificial Intelligence Sepsis Expert achieved area under the receiver operating characteristic in the range of 0.83-0.85. Performance of the Artificial Intelligence Sepsis Expert on the development and validation cohorts was indistinguishable. Using data available in the ICU in real-time, Artificial Intelligence Sepsis Expert can accurately predict the onset of sepsis in an ICU patient 4-12 hours prior to clinical recognition. A prospective study is necessary to determine the

  13. Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis.

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    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.

  14. Distribution characteristics of liquid sequestration in rats with sepsis

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    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.

  15. 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.

  16. 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.

  17. RETRACTED: Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression.

    Science.gov (United States)

    Yang, Chun-Hua; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei

  18. 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 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.

  19. Sepsis attenuates the anabolic response to skeletal muscle contraction.

    Science.gov (United States)

    Steiner, Jennifer L; Lang, Charles H

    2015-04-01

    Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ∼24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions, and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the nonstimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 (mammalian target of rapamycin [mTOR] complex 1) substrates S6K1 (70-kd ribosomal protein S6 kinase 1) Thr (8-fold), S6K1 ThrSer (7-fold) and 4E-BP1 Ser (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr (67%), S6K1 ThrSer (46%), and 4E-BP1 Ser (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr phosphorylation was decreased similarly by muscle contraction in both groups. Mitogen-activated protein kinase signaling was discordant following contraction in septic muscle; phosphorylation of extracellular signal-regulated kinase ThrTyr and p38 ThrTyr was increased similarly in both CON and CLP mice, while sepsis prevented the contraction-induced phosphorylation of JNK ThrTyr and c-JUN Ser. The expression of interleukin 6 and tumor necrosis factor α (TNF-α) mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent.

  20. Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

    DEFF Research Database (Denmark)

    Kofoed, K.

    This PhD-thesis is based on work performed at Clinical Research Centre and Department of Infectious Diseases at Copenhagen University Hospital, Hvidovre, and includes a review, a method development study, and two clinical studies. The background of the thesis is, that timely and accurate diagnosis...... 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...

  1. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    Science.gov (United States)

    Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

    2016-06-01

    Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice

    NARCIS (Netherlands)

    de Stoppelaar, Sacha F.; van 't Veer, Cornelis; Claushuis, Theodora A. M.; Albersen, Bregje J. A.; Roelofs, Joris J. T. H.; van der Poll, Tom

    2014-01-01

    Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median

  3. The Microcirculation is Preserved in Emergency Department Low‐acuity Sepsis Patients Without Hypotension

    DEFF Research Database (Denmark)

    Skibsted, Simon; Filbin, Michael; Hou, Peter

    2014-01-01

    -acuity sepsis patients. The hypothesis was that patients with sepsis, but without hypotension, will demonstrate signs of flow abnormalities compared to noninfected control patients. Methods This was a prospective, observational study in a convenience sample of patients with sepsis and noninfected controls...

  4. 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,... of Toll-like receptor responses for sepsis pathogenesis. PubmedID 18086373 Title Role of Toll-like receptor... responses for sepsis pathogenesis. Authors Weighardt H, Holzmann B. Publication

  5. 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, ...

  6. 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

  7. Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.

    Science.gov (United States)

    Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju

    2016-11-15

    Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

  8. 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

  9. Loss of Sympathetic Nerves in Spleens from Patients with End Stage Sepsis

    Directory of Open Access Journals (Sweden)

    Donald B. Hoover

    2017-12-01

    Full Text Available The spleen is an important site for central regulation of immune function by noradrenergic sympathetic nerves, but little is known about this major region of neuroimmune communication in humans. Experimental studies using animal models have established that sympathetic innervation of the spleen is essential for cholinergic anti-inflammatory responses evoked by vagal nerve stimulation, and clinical studies are evaluating this approach for treating inflammatory diseases. Most data on sympathetic nerves in spleen derive from rodent studies, and this work has established that remodeling of sympathetic innervation can occur during inflammation. However, little is known about the effects of sepsis on spleen innervation. Our primary goals were to (i localize noradrenergic nerves in human spleen by immunohistochemistry for tyrosine hydroxylase (TH, a specific noradrenergic marker, (ii determine if nerves occur in close apposition to leukocytes, and (iii determine if splenic sympathetic innervation is altered in patients who died from end stage sepsis. Staining for vesicular acetylcholine transporter (VAChT was done to screen for cholinergic nerves. Archived paraffin tissue blocks were used. Control samples were obtained from trauma patients or patients who died after hemorrhagic stroke. TH + nerves were associated with arteries and arterioles in all control spleens, occurring in bundles or as nerve fibers. Individual TH + nerve fibers entered the perivascular region where some appeared in close apposition to leukocytes. In marked contrast, spleens from half of the septic patients lacked TH + nerves fibers and the average abundance of TH + nerves for the septic group was only 16% of that for the control group (control: 0.272 ± 0.060% area, n = 6; sepsis: 0.043 ± 0.026% area, n = 8; P < 0.005. All spleens lacked cholinergic innervation. Our results provide definitive evidence for the distribution of noradrenergic

  10. Predicting Sepsis Risk Using the "Sniffer" Algorithm in the Electronic Medical Record.

    Science.gov (United States)

    Olenick, Evelyn M; Zimbro, Kathie S; DʼLima, Gabrielle M; Ver Schneider, Patricia; Jones, Danielle

    The Sepsis "Sniffer" Algorithm (SSA) has merit as a digital sepsis alert but should be considered an adjunct to versus an alternative for the Nurse Screening Tool (NST), given lower specificity and positive predictive value. The SSA reduced the risk of incorrectly categorizing patients at low risk for sepsis, detected sepsis high risk in half the time, and reduced redundant NST screens by 70% and manual screening hours by 64% to 72%. Preserving nurse hours expended on manual sepsis alerts may translate into time directed toward other patient priorities.

  11. Iron dysregulation combined with aging prevents sepsis-induced apoptosis.

    Science.gov (United States)

    Javadi, Pardis; Buchman, Timothy G; Stromberg, Paul E; Turnbull, Isaiah R; Vyas, Dinesh; Hotchkiss, Richard S; Karl, Irene E; Coopersmith, Craig M

    2005-09-01

    Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels. Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice. Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.

  12. Risk factors for fever and sepsis after percutaneous nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Aso Omer Rashid

    2016-04-01

    Conclusion: DM, staghorn stones, degree of hydronephrosis, duration of the operation and number of tracts are risk factors for post PCNL fever, while number of stones, intraoperative blood loss, duration of the operation and residual stones are risk factors for post PCNL sepsis.

  13. First report on sepsis caused by Porphyromonas pogonae.

    Science.gov (United States)

    Schröttner, Percy; Heidrich, Katharina; Rudolph, Wolfram W; Stölzel, Friedrich; Jacobs, Enno; Gunzer, Florian

    2017-04-01

    We report on a 62 year old patient who developed sepsis due to an infection caused by Porphyromonas pogonae, a recently described species of the bacterial genus Porphyromonas. This is the first case of an invasive infection with this pathogen. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Fatal sepsis by Bacillus circulans in an immunocompromised patient

    OpenAIRE

    Alebouyeh, M; Gooran Orimi, P; Azimi-rad, M; Tajbakhsh, M; Tajeddin, E; Jahani Sherafat, S; Nazemalhosseini mojarad, E; Zali, MR

    2011-01-01

    An immunosuppressed man was admitted to hospital with diarrhea and a history of urinary tract infection. He was subjected to treatment with antibiotics. The patient died of putative severe sepsis. The etiological agent was a carbapenemase producing isolate of Bacillus circulans with resistance to all prescribed antimicrobial agents.

  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

    2012-01-01

    Objective(s) 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. Materials and Methods 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. Results 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. Conclusion We conclude that procalcitonin is a better marker than CRP in the diagnosis of neonatal sepsis. PMID:23493845

  16. Rectosigmoid tubular duplication presenting as perineal sepsis in a neonate.

    Science.gov (United States)

    Zhang, Zhibo; Huang, Ying; Wang, Dajia; Su, Pengjun

    2010-03-01

    Tubular rectal duplication is a very rare congenital anomaly. We report a case of tubular rectal duplication in a newborn baby who presented with perianal sepsis. The diagnosis was confirmed by barium enema, magnetic resonance imaging, and at operation. We performed total mucosectomy through a posterior sagittal incision combined with laparotomy. The patient was doing quite well at 17-month follow-up examination.

  17. Penelitian Awal: Faktor Risiko pada Sepsis Neonatorum Awitan Dini

    Directory of Open Access Journals (Sweden)

    Rosalina D Roeslani

    2016-11-01

    Kesimpulan.Pada neonatus yang lahir di RSCM Jakarta apabila terdapat faktor risiko prematur (usia gestasi <37 minggu, dan atau nilai APGAR rendah maka harus dilakukan skrining sepsis, pemantauan ketat terhadap timbulnya SNAD, bila melakukan tindakan intervensif maka harus dengan tindakan septik-antiseptik yang ideal,serta pemberian antibiotik empiris dapat dipertimbangkan.

  18. Active Detoxification in the Treatment of Abdominal Sepsis

    Directory of Open Access Journals (Sweden)

    O. M. Shevtsova

    2009-01-01

    Full Text Available Objective: to evaluate the efficiency of extracorporeal detoxification techniques in patients with abdominal sepsis. Subjects and methods. Three hundred and seventy-nine patients with acute generalized peritonitis were examined. Extracorporeal detoxifying techniques were used during conventional therapy in Group 1 (n=319; the other patients received only traditional therapy (a control group. The time course of changes in the parameters of toxemia, a hemostasiogram, and an immunogram were examined. Results. The study indicated significantly reduced endotoxemia and better blood aggregation resulting from the use of plasmapheresis, cryoplasmasorption, and plasmasorption, as well as stimulated immunity when the above techniques were combined with autoblood photomodification and extracorporeal immunopharmacotherapy in patients with abdominal sepsis. In severe abdominal sepsis and infectious-toxic shock, there was regression of multiple organ dysfunction and lower mortality when venovenous hemofiltration was applied. Conclusion. A differential approach to using active detoxifying techniques is needed, by taking into account the severity of the disease. Key words: abdominal sepsis, detoxifying techniques.

  19. 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.

  20. Neutrophil CD64 in early-onset neonatal sepsis

    African Journals Online (AJOL)

    EL-HAKIM

    of 3.5 to 8 cases per 1,000 live births; and mortality rate 16 to 30%. Cytokines, produced by ... 40 weeks with a picture of early onset neonatal sepsis within 48 hours of life admitted to neonatal ..... Infect Dis J 2000;19 (9):879-87. 5. Gonzalez BE ...

  1. 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

    2014-07-01

    To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. The review focused primarily on pediatric literature relevant to the topic of interest. 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.

  2. Stem cells in sepsis and acute lung injury.

    Science.gov (United States)

    Cribbs, Sushma K; Matthay, Michael A; Martin, Greg S

    2010-12-01

    Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy. A directed systematic search of the medical literature using PubMed and OVID, with particular emphasis on the time period after 2002, was done to evaluate topics related to 1) the epidemiology and pathophysiology of sepsis and acute lung injury; and 2) the definition, characterization, and potential use of stem cells in these diseases. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to prospective nonrandomized clinical and preclinical studies. Stem cells have shown significant promise in the field of critical care both for 1) prognostic value and 2) treatment strategies. Although several recent studies have identified the potential benefit of stem cells in sepsis and acute lung injury, further investigations are needed to more completely understand stem cells and their potential prognostic and therapeutic value.

  3. 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 ...

  4. A Report on Antibiotic Management of Neonatal Sepsis Caused by ...

    African Journals Online (AJOL)

    This is a report on a case of neonatal sepsis and clinical management with multiple antibiotic therapy in a neonatal intensive care unit (NICU) in Brazil. A preterm baby boy was born by caesarean section at. 34 weeks and two days of gestation from an oligodramnious pregnancy with intrauterine growth restriction.

  5. Role of extracellular histones in the cardiomyopathy of sepsis.

    Science.gov (United States)

    Kalbitz, Miriam; Grailer, Jamison J; Fattahi, Fatemeh; Jajou, Lawrence; Herron, Todd J; Campbell, Katherine F; Zetoune, Firas S; Bosmann, Markus; Sarma, J Vidya; Huber-Lang, Markus; Gebhard, Florian; Loaiza, Randall; Valdivia, Hector H; Jalife, José; Russell, Mark W; Ward, Peter A

    2015-05-01

    The purpose of this study was to define the relationship in polymicrobial sepsis (in adult male C57BL/6 mice) between heart dysfunction and the appearance in plasma of extracellular histones. Procedures included induction of sepsis by cecal ligation and puncture and measurement of heart function using echocardiogram/Doppler parameters. We assessed the ability of histones to cause disequilibrium in the redox status and intracellular [Ca(2+)]i levels in cardiomyocytes (CMs) (from mice and rats). We also studied the ability of histones to disturb both functional and electrical responses of hearts perfused with histones. Main findings revealed that extracellular histones appearing in septic plasma required C5a receptors, polymorphonuclear leukocytes (PMNs), and the Nacht-, LRR-, and PYD-domains-containing protein 3 (NLRP3) inflammasome. In vitro exposure of CMs to histones caused loss of homeostasis of the redox system and in [Ca(2+)]i, as well as defects in mitochondrial function. Perfusion of hearts with histones caused electrical and functional dysfunction. Finally, in vivo neutralization of histones in septic mice markedly reduced the parameters of heart dysfunction. Histones caused dysfunction in hearts during polymicrobial sepsis. These events could be attenuated by histone neutralization, suggesting that histones may be targets in the setting of sepsis to reduce cardiac dysfunction. © FASEB.

  6. VIP as a potential therapeutic agent in gram negative sepsis.

    Science.gov (United States)

    Ibrahim, Hiba; Barrow, Paul; Foster, Neil

    2012-12-01

    Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

  7. 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...

  8. 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 ...

  9. 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 ...

  10. 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 ...

  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. 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 ...

  13. 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 ...

  14. The etiology of neonatal sepsis and patterns of antibiotic resistance

    International Nuclear Information System (INIS)

    Waheed, M.; Laeeq, A.; Maqbool, S.

    2003-01-01

    Objective: To study the patterns of causative bacteria and antibiotic resistance in neonatal sepsis. Results: Among 228 cases included in the study, the male to female ratio was 2.1 to 1. The gestational age was less than 36 weeks in 68 (30%) cases and low birth weight babies were 143 (62.6%). History of birth asphyxia was present in 103 (45%) cases. There were 142 (62.3%) cases of early onset ( 7 days). Out of 233 positive blood cultures Escherichia coli was found to be commonest (47.8%, n =111, p<0.05) both in early onset (47.8%, n=68, p <0.05) and late onset sepsis (47.3%,n=43, p<0.05). Staphylococcus aureus was the most common among gram positive organism. Resistance to cefotaxime, ceftazidime and amikacin was 34% to 80% and to ciprofloxacin 13% to 72%. A total of 64 cases (28%) died. Mortality was four times higher in early onset sespis. Conclusion: Gram negative bacteria are the commenst cause of neonatal sepsis. The resistance to the commonly used antibiotics is alarmingly high. Mortality is four times higher in early one set sepsis. (author)

  15. Haematogenous pyogenic bone and joint sepsis – reducing ...

    African Journals Online (AJOL)

    Background and objectives. Delayed presentation of haematogenous bone and joint sepsis is common in our childhood population and leads to a large burden of avoidable morbidity extending into adult life. We set out to determine causative factors in these delays. Design. A prospective study was undertaken over a 1- ...

  16. Cerebral blood flow is reduced in patients with sepsis syndrome

    International Nuclear Information System (INIS)

    Bowton, D.L.; Bertels, N.H.; Prough, D.S.; Stump, D.A.

    1989-01-01

    The relationship between sepsis-induced CNS dysfunction and changes in brain blood flow remains unknown, and animal studies examining the influence of sepsis on cerebral blood flow (CBF) do not satisfactorily address that relationship. We measured CBF and cerebrovascular reactivity to CO 2 in nine patients with sepsis syndrome using the 133 Xe clearance technique. Mean CBF was 29.6 +/- 15.8 (SD) ml/100 g.min, significantly lower than the normal age-matched value in this laboratory of 44.9 +/- 6.2 ml/100 g.min (p less than .02). This depression did not correlate with changes in mean arterial pressure. Despite the reduction in CBF, the specific reactivity of the cerebral vasculature to changes in CO 2 was normal, 1.3 +/- 0.9 ml/100 g.min/mm Hg. Brain blood flow is reduced in septic humans; the contribution of this reduction to the metabolic and functional changes observed in sepsis requires further study

  17. Procalcitonina como marcador de sepsis en niños

    Directory of Open Access Journals (Sweden)

    Diana González Rangel

    2016-04-01

    Conclusión. La procalcitonina tiene un buen rendimiento diagnóstico como marcador de sepsis en niños —con mayor utilidad cuando toma valores negativos— y buen valor pronóstico al relacionarse con mortalidad.

  18. 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.

  19. Effects of intra-abdominal sepsis on atherosclerosis in mice.

    Science.gov (United States)

    Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

    2014-09-03

    Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation. ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2

  20. Development and validation of a multiplex add-on assay for sepsis biomarkers using xMAP technology

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Schneider, Uffe Vest; Scheel, Troels

    2006-01-01

    Sepsis is a common and often fatal disease. Because sepsis can be caused by many different organisms, biomarkers that can aid in diagnosing sepsis and monitoring treatment efficacy are highly warranted. New sepsis markers may provide additional information to complement the currently used markers....

  1. 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.

  2. Barriers to implementing the Sepsis Six guidelines in an acute hospital setting.

    Science.gov (United States)

    Breen, Sarah-Jane; Rees, Sharon

    2018-05-10

    To identify the barriers to implementation of the Sepsis Six pathway. Research has suggested that compliance with the Sepsis Six pathway remains low. A convenience sample of doctors and nurses from one emergency department, two medical wards and two surgical wards were asked to complete a survey questionnaire. Data from 108 respondents were available for analysis. Doctors and nurses agreed that lack of sepsis recognition during observation rounds and failure to associate sepsis with deranged temperature and blood results acted as barriers to the identification of sepsis. Doctors and nurses agreed that nursing delays and knowledge deficits were the top barriers leading to delay in sepsis treatment. Knowledge deficits, lack of resources and practical issues were barriers identified in this survey. This will inform the educational and process needs of both doctors and nurses in order to improve sepsis care.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    PURPOSE: Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in clinical practice. We aimed to evaluate associations between hospital and patient characte....... The data indicate variations in clinical practice not explained by patient characteristics emphasizing the need for RCTs assessing fluid resuscitation volumes fluid in patients with sepsis.......PURPOSE: Fluid resuscitation is a key intervention in patients with sepsis and circulatory impairment. The recommendations for continued fluid therapy in sepsis are vague, which may result in differences in clinical practice. We aimed to evaluate associations between hospital and patient...... characteristics and fluid resuscitation volumes in ICU patients with severe sepsis. METHODS: We explored the 6S trial database of ICU patients with severe sepsis needing fluid resuscitation randomised to hydroxyethyl starch 130/0.42 vs. Ringer's acetate. Our primary outcome measure was fluid resuscitation volume...

  4. 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.

  5. 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.

  6. 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.

  7. Nursing considerations to complement the Surviving Sepsis Campaign guidelines.

    Science.gov (United States)

    Aitken, Leanne M; Williams, Ged; Harvey, Maurene; Blot, Stijn; Kleinpell, Ruth; Labeau, Sonia; Marshall, Andrea; Ray-Barruel, Gillian; Moloney-Harmon, Patricia A; Robson, Wayne; Johnson, Alexander P; Lan, Pang Nguk; Ahrens, Tom

    2011-07-01

    To provide a series of recommendations based on the best available evidence to guide clinicians providing nursing care to patients with severe sepsis. Modified Delphi method involving international experts and key individuals in subgroup work and electronic-based discussion among the entire group to achieve consensus. We used the Surviving Sepsis Campaign guidelines as a framework to inform the structure and content of these guidelines. We used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system to rate the quality of evidence from high (A) to very low (D) and to determine the strength of recommendations, with grade 1 indicating clear benefit in the septic population and grade 2 indicating less confidence in the benefits in the septic population. In areas without complete agreement between all authors, a process of electronic discussion of all evidence was undertaken until consensus was reached. This process was conducted independently of any funding. Sixty-three recommendations relating to the nursing care of severe sepsis patients are made. Prevention recommendations relate to education, accountability, surveillance of nosocomial infections, hand hygiene, and prevention of respiratory, central line-related, surgical site, and urinary tract infections, whereas infection management recommendations related to both control of the infection source and transmission-based precautions. Recommendations related to initial resuscitation include improved recognition of the deteriorating patient, diagnosis of severe sepsis, seeking further assistance, and initiating early resuscitation measures. Important elements of hemodynamic support relate to improving both tissue oxygenation and macrocirculation. Recommendations related to supportive nursing care incorporate aspects of nutrition, mouth and eye care, and pressure ulcer prevention and management. Pediatric recommendations relate to the use of antibiotics, steroids, vasopressors and

  8. 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.

  9. Pediatric Sepsis Guidelines: Summary for resource-limited countries

    Science.gov (United States)

    Khilnani, Praveen; Singhi, Sunit; Lodha, Rakesh; Santhanam, Indumathi; Sachdev, Anil; Chugh, Krishan; Jaishree, M.; Ranjit, Suchitra; Ramachandran, Bala; Ali, Uma; Udani, Soonu; Uttam, Rajiv; Deopujari, Satish

    2010-01-01

    Justification: Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa. Process: An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products. Objective: To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India. Recommendations: Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3–5 years as new body of evidence accumulates. PMID:20606908

  10. 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.

  11. 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.

  12. 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.

  13. Systemic inflammatory response syndrome criteria in defining severe sepsis.

    Science.gov (United States)

    Kaukonen, Kirsi-Maija; Bailey, Michael; Pilcher, David; Cooper, D Jamie; Bellomo, Rinaldo

    2015-04-23

    The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach. We studied data from patients from 172 intensive care units in Australia and New Zealand from 2000 through 2013. We identified patients with infection and organ failure and categorized them according to whether they had signs meeting two or more SIRS criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS-negative severe sepsis). We compared their characteristics and outcomes and assessed them for the presence of a step increase in the risk of death at a threshold of two SIRS criteria. Of 1,171,797 patients, a total of 109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis. Over a period of 14 years, these groups had similar characteristics and changes in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3% [2037 of 11,119], P<0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3% [122 of 1315], P<0.001). Moreover, this pattern remained similar after adjustment for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95% confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group, 0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted analysis, mortality increased linearly with each additional SIRS criterion (odds ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P<0.001) without any transitional increase in risk at a threshold of two SIRS criteria. The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in

  14. Arterial versus venous lactate: a measure of sepsis in children.

    Science.gov (United States)

    Samaraweera, Sahan Asela; Gibbons, Berwyck; Gour, Anami; Sedgwick, Philip

    2017-08-01

    This study assessed the agreement between arterial and venous blood lactate and pH levels in children with sepsis. This retrospective, three-year study involved 60 PICU patients, with data collected from electronic or paper patient records. The inclusion criteria comprised of children (≤17 years old) with sepsis and those who had a venous blood gas taken first with an arterial blood gas taken after within one hour. The lactate and pH values measured through each method were analysed. There is close agreement between venous and arterial lactate up to 2 mmol/L. As this value increases, this agreement becomes poor. The limits of agreement (LOA) are too large (±1.90 mmol/L) to allow venous and arterial lactate to be used interchangeably. The mean difference and LOA between both methods would be much smaller if derived using lactate values under 2.0 mmol/L. There is close agreement between arterial and venous pH (MD = -0.056, LOA ± 0.121). However, due to extreme variations in pH readings during sepsis, pH alone is an inadequate marker. A venous lactate ≤2 mmol/L can be used as a surrogate for arterial lactate during early management of sepsis in children. However, if the value exceeds 2 mmol/L, an arterial sample must confirm the venous result. What is known: • In children with septic shock, a blood gas is an important test to show the presence of acidosis and high lactic acid. Hyperlactataemia on admission is an early predictor of outcome and is associated with a greater mortality risk. • An arterial sample is the standard for lactate measurement, however getting a sample may be challenging in the emergency department or a general paediatric ward. Venous samples are quicker and easier to obtain. Adult studies generally advise caution in replacing venous lactate values for the arterial standard, whilst paediatric studies are limited in this area. What is new: • This is the first study assessing the agreement between arterial and peripheral venous

  15. Bioinformatical Analysis of Organ-Related (Heart, Brain, Liver, and Kidney and Serum Proteomic Data to Identify Protein Regulation Patterns and Potential Sepsis Biomarkers

    Directory of Open Access Journals (Sweden)

    Andreas Hohn

    2018-01-01

    Full Text Available During the last years, proteomic studies have revealed several interesting findings in experimental sepsis models and septic patients. However, most studies investigated protein alterations only in single organs or in whole blood. To identify possible sepsis biomarkers and to evaluate the relationship between protein alteration in sepsis affected organs and blood, proteomics data from the heart, brain, liver, kidney, and serum were analysed. Using functional network analyses in combination with hierarchical cluster analysis, we found that protein regulation patterns in organ tissues as well as in serum are highly dynamic. In the tissue proteome, the main functions and pathways affected were the oxidoreductive activity, cell energy generation, or metabolism, whereas in the serum proteome, functions were associated with lipoproteins metabolism and, to a minor extent, with coagulation, inflammatory response, and organ regeneration. Proteins from network analyses of organ tissue did not correlate with statistically significantly regulated serum proteins or with predicted proteins of serum functions. In this study, the combination of proteomic network analyses with cluster analyses is introduced as an approach to deal with high-throughput proteomics data to evaluate the dynamics of protein regulation during sepsis.

  16. Degree of agreement among sepsis diagnosis criteria in adult emergency room patients with infection

    Science.gov (United States)

    Sinto, R.; Chandra, A. T.; Lie, K. C.; Suwarto, S.

    2018-03-01

    The study on the degree of agreement among three established sepsis diagnosis criteria become the necessity to investigate the best sepsis diagnosis criteria in Indonesia further. A cross-sectional study of adult Emergency Room patients hospitalized with a diagnosis of infection in CiptoMangunkusumo Hospital, Indonesia was conducted during March and April 2017. We recorded diagnosis, gender, age, comorbidities, infection source, and origin. Every subject was classified into sepsis and non-sepsis based on 1991, 2001 and sepsis-3 criteria. Raw % and Kappa agreement coefficients (κ) were calculated according to previously established formula to measure the degree of agreement among three diagnostic criteria. As many as 278 subjects were included in this study. The raw % agreement and κ between 1991 and 2001 criteria is 69.07% and 0.34 respectively. The raw % agreement and κ between 2001 and sepsis-3 criteria is 56.12% and 0.15 respectively. The raw % agreement and κ between 1991 and sepsis-3 criteria is 48.19% and -0.02. In conclusions, there is afair agreement between 1991 and 2001 criteria, poor agreement between 2001 and sepsis-3 criteria, and poor disagreement between 1991 and sepsis-3 criteria. This necessitates further Indonesian study of the best diagnosis criteria to diagnose an infected patient with sepsis.

  17. CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Balázs Csóka

    2009-07-01

    Full Text Available Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB(2 receptors on immune cells. Here we examined the role of CB(2 receptors in regulating the host's response to sepsis.The role of CB(2 receptors was studied by subjecting CB(2 receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB(2 receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB(2 receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF-kappaB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB(2 receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b(+ and CD19(+ cells during CLP.Taken together, our results establish for the first time that CB(2 receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2 receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.

  18. Reporting of Sepsis Cases for Performance Measurement Versus for Reimbursement in New York State.

    Science.gov (United States)

    Prescott, Hallie C; Cope, Tara M; Gesten, Foster C; Ledneva, Tatiana A; Friedrich, Marcus E; Iwashyna, Theodore J; Osborn, Tiffany M; Seymour, Christopher W; Levy, Mitchell M

    2018-05-01

    Under "Rory's Regulations," New York State Article 28 acute care hospitals were mandated to implement sepsis protocols and report patient-level data. This study sought to determine how well cases reported under state mandate align with discharge records in a statewide administrative database. Observational cohort study. First 27 months of mandated sepsis reporting (April 1, 2014, to June 30, 2016). Hospitalizations with sepsis at New York State Article 28 acute care hospitals. Sepsis regulations with mandated reporting. We compared cases reported to the New York State Department of Health Sepsis Clinical Database with discharge records in the Statewide Planning and Research Cooperative System database. We classified discharges as 1) "coded sepsis discharges"-a diagnosis code for severe sepsis or septic shock and 2) "possible sepsis discharges," using Dombrovskiy and Angus criteria. Of 111,816 sepsis cases reported to the New York State Department of Health Sepsis Clinical Database, 105,722 (94.5%) were matched to discharge records in Statewide Planning and Research Cooperative System. The percentage of coded sepsis discharges reported increased from 67.5% in the first quarter to 81.3% in the final quarter of the study period (mean, 77.7%). Accounting for unmatched cases, as many as 82.7% of coded sepsis discharges were potentially reported, whereas at least 17.3% were unreported. Compared with unreported discharges, reported discharges had higher rates of acute organ dysfunction (e.g., cardiovascular dysfunction 63.0% vs 51.8%; p New York State Department of Health Sepsis Clinical Database. Incomplete reporting appears to be driven more by underrecognition than attempts to game the system, with minimal bias to risk-adjusted hospital performance measurement.

  19. Sepsis Induces a Dysregulated Neutrophil Phenotype That Is Associated with Increased Mortality

    Directory of Open Access Journals (Sweden)

    Jaimin M. Patel

    2018-01-01

    Full Text Available Background. Neutrophil dysfunction in sepsis has been implicated in the pathogenesis of multiorgan failure; however, the role of neutrophil extracellular traps (NETs remains uncertain. We aimed to determine the sequential changes in ex vivo NETosis and its relationship with mortality in patients with sepsis and severe sepsis. Methods. This was a prospective observational cohort study enrolling 21 healthy age-matched controls and 39 sepsis and 60 severe sepsis patients from acute admissions to two UK hospitals. Patients had sequential bloods for the ex vivo assessment of NETosis in response to phorbol-myristate acetate (PMA using a fluorometric technique and chemotaxis using time-lapse video microscopy. Continuous data was tested for normality, with appropriate parametric and nonparametric tests, whilst categorical data was analysed using a chi-squared test. Correlations were performed using Spearman’s rho. Results. Ex vivo NETosis was reduced in patients with severe sepsis, compared to patients with sepsis and controls (p=0.002. PMA NETosis from patients with septic shock was reduced further (p<0.001 compared to controls. The degree of metabolic acidosis correlated with reduced NETosis (p<0.001, and this was replicated when neutrophils from healthy donors were incubated in acidotic media. Reduced NETosis at baseline was associated with an increased 30-day (p=0.002 and 90-day mortality (p=0.014 in sepsis patients. These findings were accompanied by defects in neutrophil migration and delayed apoptosis. Resolution of sepsis was not associated with the return to baseline levels of NETosis or migration. Conclusions. Sepsis induces significant changes in neutrophil function with the degree of dysfunction corresponding to the severity of the septic insult which persists beyond physiological recovery from sepsis. The changes induced lead to the failure to effectively contain and eliminate the invading pathogens and contribute to sepsis

  20. 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......') oscillations were absent in 9% and 22% of the patients, respectively. In patients in whom spontaneous blood pressure oscillations were preserved, the MF' oscillations occurred at 0.021 Hz (median, interquartile range 0.013-0.030), whereas the LF' oscillations occurred at 0.009 Hz (median, interquartile range 0...

  1. Platelets and Multi-Organ Failure in Sepsis

    Directory of Open Access Journals (Sweden)

    Elisabetta Greco

    2017-10-01

    Full Text Available Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

  2. Platelets and Multi-Organ Failure in Sepsis.

    Science.gov (United States)

    Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

    2017-10-20

    Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

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

    Directory of Open Access Journals (Sweden)

    Rajapakse Senaka

    2009-01-01

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

  4. Flavobacterium meningosepticum sepsis in an infant with a diarrheal prodrome.

    Science.gov (United States)

    Springer, S C; Johnson, G M

    1999-02-01

    A full term, previously normal 2 1/2-month-old black boy was transferred to our hospital from an outlying facility on hospital day 5 for failure to thrive. Three weeks before transfer, the infant was hospitalized for a diarrheal illness with fever. The baby received 3 days of ceftriaxone empirically and was discharged home after the sepsis evaluation was negative. Mild diarrhea and steady weight loss continued and the baby was readmitted. Blood culture done on admission grew Flavobacterium meningosepticum, an organism previously described as an uncommon cause of sepsis in neonates and immunocompromised individuals. As it is water-borne, it has been associated with infection via contaminated water. This organism is usually resistant to antibiotics commonly used for empiric treatment. To our knowledge, this is the first reported case of Flavobacterium bacteremia associated with a prodromal and concurrent diarrheal illness.

  5. Colostomy for Perianal Sepsis With Ecthyma Gangrenosum in Immunocompromised Children.

    Science.gov (United States)

    Vuille-dit-Bille, Raphael N; Berger, Christoph; Meuli, Martin; Grotzer, Michael A

    2016-01-01

    Perianal sepsis with ecthyma gangrenosum is a severe and potentially mutilating complication in immunocompromised children. Therapies include antimicrobial treatment, incision and drainage, generous tissue debridement, and skin transplantation. We describe 3 children with acute lymphoblastic leukemia having sepsis with Pseudomonas aeruginosa in febrile neutropenia and severe perianal infections treated relatively early with a protective colostomy. Indications for colostomy were nonhealing wounds, and ceaseless pain. All patients showed a rapid reduction of pain. Complete wound healing was seen in 2 patients, and considerable pain reduction and increased quality of life were seen in a third patient during palliative care. These results suggest that a protective colostomy should be considered early in the management of immunocompromised children with ecthyma gangrenosum.

  6. Association between sepsis and Rocky Mountain spotted fever.

    Science.gov (United States)

    Bacci, Marcelo Rodrigues; Namura, José Jorge

    2012-12-06

    Rocky Mountain spotted fever (RMSF) is a disease caused by the Gram-negative coccobacillus Rickettsia ricketsii which has been on the rise since the last decade in the USA. The symptoms are common to the many viral diseases, and the classic triad of fever, rash and headache is not always present when RMSF is diagnosed. It may progress to severe cases such as renal failure, disseminated intravascular coagulation and septicaemia. This report aims to present a fulminant case of RMSF associated with sepsis. It describes a female patient's case that quickly progressed to sepsis and death. The patient showed non-specific symptoms for 5 days before being admitted to a hospital. The fact that she lived in an area highly infested with Amblyomma aureolatum ticks was unknown to the medical staff until the moment she died.

  7. Dress syndrome with sepsis, acute respiratory distress syndrome and pneumomediastinum

    Directory of Open Access Journals (Sweden)

    Prabhas Prasun Giri

    2011-01-01

    Full Text Available Drug rash with eosinophilia and systemic symptoms (DRESS syndrome reflects a serious hypersensitivity reaction to drugs, and is characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause DRESS syndrome. We report a case of a 10-year-old girl who developed clinical manifestations of fever, rash, lymphadenopathy, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis after taking phenobarbital for seizures, with subsequent development of sepsis, acute respiratory distress syndrome (ARDS and spontaneous air leak syndrome (pnemothorax and pneumomediastinum. She was put on steroids and various antibiotics and was ventilated, but ultimately succumbed to sepsis and pulmonary complications.

  8. Efficacy of Enrofloxacin in a Mouse Model of Sepsis

    OpenAIRE

    Slate, Andrea R; Bandyopadhyay, Sheila; Francis, Kevin P; Papich, Mark G; Karolewski, Brian; Hod, Eldad A; Prestia, Kevin A

    2014-01-01

    We examined the efficacy of enrofloxacin administered by 2 different routes in a mouse model of sepsis. Male CD1 mice were infected with a bioluminescent strain of enteropathogenic Escherichia coli and treated with enrofloxacin either by injection or in drinking water. Peak serum levels were evaluated by using HPLC. Mice were monitored for signs of clinical disease, and infections were monitored by using bioluminescence imaging. Serum levels of enrofloxacin and the active metabolite ciproflox...

  9. Effect of bacterial sepsis on gluconeogenic capacity in the rat

    International Nuclear Information System (INIS)

    Holman, J.M. Jr.; Saba, T.M.

    1988-01-01

    Since sepsis places increased demands on the host for energy and on other substrates for tissue repair and host defense, hepatic gluconeogenesis is critical for the host's adaptation to sepsis. Substrate-stimulated gluconeogenesis (i.e., gluconeogenic capacity) was assessed by the alanine load method in mannoheptulose-pretreated rats made septic by cecal ligation after laparotomy, as well as by cecal ligation and puncture after laparotomy. Fasted rats subjected to laparotomy only (sham-ligated) and fasted, nonoperated rats (controls) were investigated simultaneously. Following an overnight (-18 to 0 hr) fast, nonoperated animals converted 17.9 +/- 1.5% of [ 14 C]alanine to [ 14 C]glucose. Continued fasting in nonoperated animals resulted in enhanced (P less than 0.05) gluconeogenic capacity (6 hr = 27.2 +/- 3.0%; 24 hr = 26.2 +/- 1.9%; and 48 hr = 28.5 +/- 2.6%) relative to Time 0. Laparotomy alone (sham ligation) delayed the fasting-induced increase (P less than 0.05) in gluconeogenesis capacity (6 hr = 21.1 +/- 1.2%; 24 hr = 18.5 +/- 1.3%; 48 hr = 27.8 +/- 1.0%) relative to Time 0. In contrast, postoperative sepsis produced a sustained depression (P less than 0.05) of gluconeogenic capacity relative to nonoperated sham-ligated controls at 48 hr (cecal ligation, 18.4 +/- 1.4%; and cecal ligation and puncture, 18.8 +/- 1.2%). Thus, (1) fasting enhances hepatic gluconeogenic capacity; (2) surgical trauma transiently blunts the gluconeogenic response to fasting; and (3) sepsis undermines the gluconeogenic response to fasting

  10. Extracorporeal therapy in sepsis: are we there yet?

    Science.gov (United States)

    Shukla, Ashutosh M

    2012-02-01

    The role of extracorporeal therapies (ECTs) in sepsis is unclear and is a strongly debated topic in critical-care medicine. Unfortunately, much of this debate arises because we lack a clear understanding of what defines the stage and severity of the disease, and the pivotal pathophysiological events dictating outcomes. In the absence of this knowledge, ECTs remain among a large group of therapies with high promise but unproven efficacy.

  11. [Sepsis in neonate, A 291 cases study (author's transl)].

    Science.gov (United States)

    Lozano Giménez, C; Gómez-Taylor, J C; Otero, M C; Fernández-Gilino, C; Mascarós, E

    1979-02-01

    A four-year experience with sepsis in the neonate is described. Clinical picture, laboratory data and mortality of 291 newborn, aged 0-28 days, are analyzed. The rise in the incidence of septicemia in the group of newborn with clinical onset within the first 24 hours of life and the preterm 5. degrees to 9. degrees day of life, was commented. The need to develop a more effective profilaxis toward the reduction of morbidity and mortality is emphasized.

  12. Association Among Blood Transfusion, Sepsis, and Decreased Long-term Survival After Colon Cancer Resection.

    Science.gov (United States)

    Aquina, Christopher T; Blumberg, Neil; Becerra, Adan Z; Boscoe, Francis P; Schymura, Maria J; Noyes, Katia; Monson, John R T; Fleming, Fergal J

    2017-08-01

    To investigate the potential additive effects of blood transfusion and sepsis on colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival after colon cancer surgery. Perioperative blood transfusions are associated with infectious complications and increased risk of cancer recurrence through systemic inflammatory effects. Furthermore, recent studies have suggested an association among sepsis, subsequent systemic inflammation, and adverse cardiovascular outcomes. However, no study has investigated the association among transfusion, sepsis, and disease-specific survival in postoperative patients. The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I to III colon cancer resections from 2004 to 2011. Propensity-adjusted survival analyses assessed the association of perioperative allogeneic blood transfusion, sepsis, and 5-year colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival. Among 24,230 patients, 29% received a transfusion and 4% developed sepsis. After risk adjustment, transfusion and sepsis were associated with worse colon cancer disease-specific survival [(+)transfusion: hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.09-1.30; (+)sepsis: HR 1.84, 95% CI 1.44-2.35; (+)transfusion/(+)sepsis: HR 2.27, 95% CI 1.87-2.76], cardiovascular disease-specific survival [(+)transfusion: HR 1.18, 95% CI 1.04-1.33; (+)sepsis: HR 1.63, 95% CI 1.14-2.31; (+)transfusion/(+)sepsis: HR 2.04, 95% CI 1.58-2.63], and overall survival [(+)transfusion: HR 1.21, 95% CI 1.14-1.29; (+)sepsis: HR 1.76, 95% CI 1.48-2.09; (+)transfusion/(+)sepsis: HR 2.36, 95% CI 2.07-2.68] relative to (-)transfusion/(-)sepsis. Additional analyses suggested an additive effect with those who both received a blood transfusion and developed sepsis having even worse survival. Perioperative blood transfusions are associated with shorter survival

  13. Maternal epidural use and neonatal sepsis evaluation in afebrile mothers.

    Science.gov (United States)

    Goetzl, L; Cohen, A; Frigoletto, F; Ringer, S A; Lang, J M; Lieberman, E

    2001-11-01

    Epidural use has been associated with a higher rate of neonatal sepsis evaluation. Epidural-related fever explains some of the increase but not the excess of neonatal sepsis evaluations in afebrile women We studied 1109 women who had singleton term pregnancies and who presented in spontaneous labor and were afebrile during labor (24 hours or sustained fetal heart rate of >160 beats per minute. Minor criteria included a maternal temperature of 99.6 degrees F to 100.4 degrees F, rupture of membranes for 12 to 24 hours, maternal admission white blood cell count of >15 000 cells/mL(3), or an Apgar score of 24 hours (6.2% vs 3.4%), low-grade fever of 99.6 degrees F to 100.4 degrees F (24.3% vs 5.2%), and rupture of membranes for 12 to 24 hours (21.4% vs 5.2%) than women without epidural. Epidural analgesia is associated with increased rates of major and minor criteria for neonatal sepsis evaluations in afebrile women.

  14. Complement activation in emergency department patients with severe sepsis.

    Science.gov (United States)

    Younger, John G; Bracho, David O; Chung-Esaki, Hangyul M; Lee, Moonseok; Rana, Gurpreet K; Sen, Ananda; Jones, Alan E

    2010-04-01

    This study assessed the extent and mechanism of complement activation in community-acquired sepsis at presentation to the emergency department (ED) and following 24 hours of quantitative resuscitation. A prospective pilot study of patients with severe sepsis and healthy controls was conducted among individuals presenting to a tertiary care ED. Resuscitation, including antibiotics and therapies to normalize central venous and mean arterial pressure (MAP) and central venous oxygenation, was performed on all patients. Serum levels of Factor Bb (alternative pathway), C4d (classical and mannose-binding lectin [MBL] pathway), C3, C3a, and C5a were determined at presentation and 24 hours later among patients. Twenty patients and 10 healthy volunteer controls were enrolled. Compared to volunteers, all proteins measured were abnormally higher among septic patients (C4d 3.5-fold; Factor Bb 6.1-fold; C3 0.8-fold; C3a 11.6-fold; C5a 1.8-fold). Elevations in C5a were most strongly correlated with alternative pathway activation. Surprisingly, a slight but significant inverse relationship between illness severity (by sequential organ failure assessment [SOFA] score) and C5a levels at presentation was noted. Twenty-four hours of structured resuscitation did not, on average, affect any of the mediators studied. Patients with community-acquired sepsis have extensive complement activation, particularly of the alternative pathway, at the time of presentation that was not significantly reversed by 24 hours of aggressive resuscitation.

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

    Directory of Open Access Journals (Sweden)

    Chiu-Yin Yeh

    2016-03-01

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

  16. Sinusitis and intracranial sepsis: the CT imaging and clinical presentation

    International Nuclear Information System (INIS)

    Saxton, V.J.; Boldt, D.W.; Shield, L.K.

    1995-01-01

    The CT imaging and clinical presentation in 14 children with coexistent intracranial sepsis and sinusitis were reviewed. A routine CT head scan (10-mm thick semi-axial slices through the cranium done before and after intravenous contrast medium administration) was found to be an inadequate initial investigation as the intracranial collection was missed in four patients and the abnormal sinuses not shown in six. In half the children the dagnosis of sinusitis was unsuspected at the time of admission. The dominant clinical features were fever, intense headache and facial swelling in early adolescent males. In this clinical setting we recommend: (1) The routine scan is extended through the frontal and ethmoidal sinuses and photographed at a window level and width showing both bone detail and air/soft tissue interfaces; (2) direct coronal projections are performed through the anterior cranial fossa if no collection is seen on the routine study; (3) an early repeat scan within 48 h if the initial study shows no intracranial pathology but the fronto-ethomoidal sinuses are abnormal and there is a high clinical supicion of intracranial sepsis; and (4) in the presence of intracranial sepsis the vault is viewed at bone window settings to exclude cranial osteomyelitis. (orig.)

  17. Role of human recombinant activated protein C and low dose corticosteroid therapy in sepsis

    Directory of Open Access Journals (Sweden)

    Aparna Shukla

    2010-01-01

    Full Text Available Despite advances in modern medicine, sepsis remains a complex syndrome that has been associated with significant morbidity and mortality. Multiple organ failure associated with sepsis leads to high mortality and morbidity. About 28 - 50% deaths have been reported in patients with sepsis. The number of sepsis patients is increasing, with considerable burden on healthcare facilities. Various factors leading to a rise in the incidence of sepsis are (1 Improvement of diagnostic procedures (2 Increase in the number of immunocompromised patients taking treatment for various autoimmune disease, carcinomas, organ transplantation (3 Advances in intensive procedures (4 Nosocomial infections (5 Extensive use of antibiotics. With the better understanding of sepsis various modalities to modify pathophysiological response of septic patients have developed. Activated protein C and low-dose corticosteroid therapy have been tried in patients, with variable results.

  18. The Rate of Sepsis in a National Pediatric Population, 2006 to 2012.

    Science.gov (United States)

    Schuller, Kristin A; Hsu, Benson S; Thompson, Allyson B

    2017-10-01

    The rate of pediatric severe sepsis is reported to be on the rise in the United States, increasing by approximately 6000 cases annually. The goal of this study was to determine the rate of pediatric sepsis per 100 000 inpatient discharges over time. The 2006, 2009, and 2012 Agency for Healthcare Research and Quality Healthcare Cost Utilization Project Kid's Inpatient Databases were used to analyze the rate of sepsis in children over time. The rate of pediatric sepsis has increased over time from 92.8 per 100 000 in 2006 to 158.7 per 100 000 in 2012. Children less than a year old with Medicaid coverage and 3 or more procedures during hospitalization have significantly higher rates than their counterparts. This study helps clarify the population demographics that are at greater risk for sepsis infections. Understanding the at-risk population aids policymakers and care providers in targeting these populations and make drastic changes to sepsis policies.

  19. Central-peripheral Temperature Monitoring as a Marker for Diagnosing Late-onset Neonatal Sepsis.

    Science.gov (United States)

    Leante-Castellanos, José Luis; Martínez-Gimeno, Antonio; Cidrás-Pidré, Manuel; Martínez-Munar, Gerardo; García-González, Ana; Fuentes-Gutiérrez, Carmen

    2017-12-01

    The prognosis for late-onset sepsis depends largely on a timely diagnosis. We assess central-peripheral temperature difference monitoring as a marker for late-onset neonatal sepsis diagnosis. We performed a prospective, observational study focusing on a cohort of 129 very low-birth-weight infants. Thermal gradient alteration was defined as a difference of > 2°C maintained during 4 hours. We then determined its association with the late-onset sepsis variable through logistic regression. We enrolled 129 preterm babies in 52 months. Thermal gradient alterations showed an adjusted odds ratio for late-onset sepsis of 23.60 (95% confidence interval [CI], 6.80-81.88), with a sensitivity of 83% and negative predictive value of 94%. In 71% of cases, thermal gradient alteration was the first clinical sign of sepsis, while C-reactive protein was peripheral temperature differences are an early sign of evolving late-onset sepsis.

  20. Dynamics of hepatic gene expression and serum cytokine profiles in single and double-hit burn and sepsis animal models

    Directory of Open Access Journals (Sweden)

    Rohit Rao

    2015-06-01

    Full Text Available We simulate the pathophysiology of severe burn trauma and burn-induced sepsis, using rat models of experimental burn injury and cecal ligation and puncture (CLP either individually (singe-hit model or in combination (double-hit model. The experimental burn injury simulates a systemic but sterile pro-inflammatory response, while the CLP simulates the effect of polymicrobial sepsis. Given the liver׳s central role in mediating the host immune response and onset of hypermetabolism after burn injury, elucidating the alterations in hepatic gene expression in response to injury can lead to a better understanding of the regulation of the inflammatory response, whereas circulating cytokine protein expression, reflects key systemic inflammatory mediators. In this article, we present both the hepatic gene expression and circulating cytokine/chemokine protein expression data for the above-mentioned experimental model to gain insights into the temporal dynamics of the inflammatory and hypermetabolic response following burn and septic injury. This data article supports results discussed in research articles (Yang et al., 2012 [1,4]; Mattick et al. 2012, 2013 [2,3]; Nguyen et al., 2014 [5]; Orman et al., 2011, 2012 [6–8].

  1. Effects of volume resuscitation on the microcirculation in animal models of lipopolysaccharide sepsis: a systematic review

    OpenAIRE

    Obonyo, Nchafatso G.; Fanning, Jonathon P.; Ng, Angela S. Y.; Pimenta, Leticia P.; Shekar, Kiran; Platts, David G.; Maitland, Kathryn; Fraser, John F.

    2016-01-01

    Background Recent research has identified an increased rate of mortality associated with fluid bolus therapy for severe sepsis and septic shock, but the mechanisms are still not well understood. Fluid resuscitation therapy administered for sepsis and septic shock targets restoration of the macro-circulation, but the pathogenesis of sepsis is complex and includes microcirculatory dysfunction. Objective The objective of the study is to systematically review data comparing the effects of differe...

  2. The Surviving Sepsis Campaign: Where have we been and where are we going?

    Science.gov (United States)

    Dellinger, R Phillip

    2015-04-01

    The Surviving Sepsis Campaign develops and promotes evidence-based guidelines and performance-improvement practices aimed at reducing deaths from sepsis worldwide. The most recent guidelines, published in 2013, provide detailed management strategies for acute care, fluid resuscitation, and vasopressor use. In addition, the campaign has developed simple, short protocols for what to do within 3 and 6 hours of recognition of sepsis. These protocols are associated with reduced mortality rates. Copyright © 2015 Cleveland Clinic.

  3. Early management of sepsis with emphasis on early goal directed therapy: AME evidence series 002

    OpenAIRE

    Zhang, Zhongheng; Hong, Yucai; Smischney, Nathan J.; Kuo, Han-Pin; Tsirigotis, Panagiotis; Rello, Jordi; Kuan, Win Sen; Jung, Christian; Robba, Chiara; Taccone, Fabio Silvio; Leone, Marc; Spapen, Herbert; Grimaldi, David; Van Poucke, Sven; Simpson, Steven Q.

    2017-01-01

    Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on seps...

  4. Sepsis Definitions: The Search for Gold and What CMS Got Wrong.

    Science.gov (United States)

    Kalantari, Annahieta; Mallemat, Haney; Weingart, Scott D

    2017-08-01

    On October 1, 2015, the United States Centers for Medicare and Medicaid Services (CMS) issued a core measure addressing the care of septic patients. These core measures are controversial among healthcare providers. This article will address that there is no gold standard definition for sepsis, severe sepsis or septic shock and the CMS-assigned definitions for severe sepsis and septic shock are premature and inconsistent with evidence-based definitions.

  5. Determinants of Carboxyhemoglobin Levels and Relationship with Sepsis in a Retrospective Cohort of Preterm Neonates

    OpenAIRE

    McArdle, Andrew J.; Webbe, James; Sim, Kathleen; Parrish, Graham; Hoggart, Clive; Wang, Yifei; Kroll, J. Simon; Godambe, Sunit; Cunnington, Aubrey J.

    2016-01-01

    Carboxyhemoglobin levels in blood reflect endogenous carbon monoxide production and are often measured during routine blood gas analysis. Endogenous carbon monoxide production has been reported to be increased during sepsis, but carboxyhemoglobin levels have not been thoroughly evaluated as a biomarker of sepsis. We sought to determine whether carboxyhemoglobin levels were elevated during sepsis in a high risk population of premature neonates. We conducted a retrospective cohort study of 30 i...

  6. Treating a 20 mm Hg gradient alleviates myocardial hypertrophy in experimental aortic coarctation.

    Science.gov (United States)

    Wendell, David C; Friehs, Ingeborg; Samyn, Margaret M; Harmann, Leanne M; LaDisa, John F

    2017-10-01

    Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 × 14-cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. LV mass was elevated for CoA (5.2 ± 0.55 g) versus control (3.6 ± 0.16 g) and corrected (4.0 ± 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV's perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A POCT platform for sepsis biomarkers (Conference Presentation)

    Science.gov (United States)

    Baldini, Francesco; Adinolfi, Barbara; Berneschi, Simone; Bernini, Romeo; Giannetti, Ambra; Grimaldi, Immacolata Angelica; Persichetti, Gianluca; Testa, Genni; Tombelli, Sara; Trono, Cosimo

    2017-06-01

    Infectious diseases and sepsis, as a severe and potential medical condition in which the immune system overreacts and finally turns against itself, are a worldwide problem. As a matter of fact, it is considered the main cause of mortality in intensive care. For such a pathology, a timely diagnosis is essential, since it has been shown that each hour of delay in the administration of an effective pharmacological treatment increases the mortality rate of 7%. Therefore, the advent of a POCT platform for sepsis is highly requested by physicians. Biomarkers have gained importance for the diagnosis and treatment monitoring of septic patients, since biomarkers can indicate the severity of sepsis and can differentiate bacterial from viral and fungal infection, and systemic sepsis from local infection. The present paper deals with the development of fluorescence-based bioassays for the sepsis biomarkers and their integration on a multianalyte chip. Among the different biomarker candidates, the attention was focused on procalcitonin (PCT), C-reactive protein (CRP) and interleukine-6 (IL-6) as well as on soluble urokinase plasminogen activator receptor (suPAR) recently proposed as a very effective inflammatory marker, potentially capable of acting also as a prognostic biomarker. Starting point of this new setup was an already developed fluorescence-based optical platform, which makes use of multichannel polymethylmetacrylate chips for the detection of different bioanalytes, and the serial interrogation of the microfluidic channels of the chip. The novel proposed optical setup makes use of a suitable fluorescence excitation and detection scheme, capable of performing the simultaneous interrogation of all the channels. For the excitation part of the optical setup, a diffractive optical element is used which generates a pattern of parallel lines, for the simultaneous excitation of all the channels and for the optimization of the optical power distribution. For the detection part

  8. In Search of a Cure for Sepsis: Taming the Monster in Critical Care Medicine.

    Science.gov (United States)

    Okeke, Emeka B; Uzonna, Jude E

    2016-01-01

    In spite of over half a century of research, sepsis still constitutes a major problem in health care delivery. Although advances in research have significantly increased our knowledge of the pathogenesis of sepsis and resulted in better prognosis and improved survival outcome, sepsis still remains a major challenge in modern medicine with an increase in occurrence predicted and a huge socioeconomic burden. It is generally accepted that sepsis is due to an initial hyperinflammatory response. However, numerous efforts aimed at targeting the proinflammatory cytokine network have been largely unsuccessful and the search for novel potential therapeutic targets continues. Recent studies provide compelling evidence that dysregulated anti-inflammatory responses may also contribute to sepsis mortality. Our previous studies on the role of regulatory T cells and phosphoinositide 3-kinases in sepsis highlight immunological approaches that could be explored for sepsis therapy. In this article, we review the current and emerging concepts in sepsis, highlight novel potential therapeutic targets and immunological approaches for sepsis treatment and propose a biphasic treatment approach for management of the condition. © 2016 S. Karger AG, Basel.

  9. Designing and testing computer based screening engine for severe sepsis/septic shock.

    Science.gov (United States)

    Herasevich, V; Afessa, B; Chute, C G; Gajic, O

    2008-11-06

    This study addresses the role of a sepsis "sniffer", an automatic screening tool for the timely identification of patients with severe sepsis/septic shock, based electronic medical records. During the two months prospective implementation in a medical intensive care unit, 37 of 320 consecutive patients developed severe sepsis/septic shock. The sniffer demonstrated a sensitivity of 48% and specificity of 86%, and positive predictive value 32%. Further improvements are needed prior to the implementation of sepsis sniffer in clinical practice and research.

  10. Septris: a novel, mobile, online, simulation game that improves sepsis recognition and management.

    Science.gov (United States)

    Evans, Kambria H; Daines, William; Tsui, Jamie; Strehlow, Matthew; Maggio, Paul; Shieh, Lisa

    2015-02-01

    Annually affecting over 18 million people worldwide, sepsis is common, deadly, and costly. Despite significant effort by the Surviving Sepsis Campaign and other initiatives, sepsis remains underrecognized and undertreated. Research indicates that educating providers may improve sepsis diagnosis and treatment; thus, the Stanford School of Medicine has developed a mobile-accessible, case-based, online game entitled Septris (http://med.stanford.edu/septris/). Septris, launched online worldwide in December 2011, takes an innovative approach to teaching early sepsis identification and evidence-based management. The free gaming platform leverages the massive expansion over the past decade of smartphones and the popularity of noneducational gaming.The authors sought to assess the game's dissemination and its impact on learners' sepsis-related knowledge, skills, and attitudes. In 2012, the authors trained Stanford pregraduate (clerkship) and postgraduate (resident) medical learners (n = 156) in sepsis diagnosis and evidence-based practices via 20 minutes of self-directed game play with Septris. The authors administered pre- and posttests. By October 2014, Septris garnered over 61,000 visits worldwide. After playing Septris, both pre- and postgraduate groups improved their knowledge on written testing in recognizing and managing sepsis (P game scores with sepsis knowledge.

  11. Early Prediction of Sepsis Incidence in Critically Ill Patients Using Specific Genetic Polymorphisms.

    Science.gov (United States)

    David, Vlad Laurentiu; Ercisli, Muhammed Furkan; Rogobete, Alexandru Florin; Boia, Eugen S; Horhat, Razvan; Nitu, Razvan; Diaconu, Mircea M; Pirtea, Laurentiu; Ciuca, Ioana; Horhat, Delia; Horhat, Florin George; Licker, Monica; Popovici, Sonia Elena; Tanasescu, Sonia; Tataru, Calin

    2017-06-01

    Several diagnostic methods for the evaluation and monitoring were used to find out the pro-inflammatory status, as well as incidence of sepsis in critically ill patients. One such recent method is based on investigating the genetic polymorphisms and determining the molecular and genetic links between them, as well as other sepsis-associated pathophysiologies. Identification of genetic polymorphisms in critical patients with sepsis can become a revolutionary method for evaluating and monitoring these patients. Similarly, the complications, as well as the high costs associated with the management of patients with sepsis, can be significantly reduced by early initiation of intensive care.

  12. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

    Science.gov (United States)

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  13. Circulating Long Noncoding RNAs as Potential Biomarkers of Sepsis: A Preliminary Study.

    Science.gov (United States)

    Dai, Yu; Liang, Zhixin; Li, Yulin; Li, Chunsun; Chen, Liangan

    2017-11-01

    Long noncoding RNAs (lncRNAs) are becoming promising biomarker candidates in various diseases as assessed via sequencing technologies. Sepsis is a life-threatening disease without ideal biomarkers. The aim of this study was to investigate the expression profile of lncRNAs in the peripheral blood of sepsis patients and to find potential biomarkers of sepsis. A lncRNA expression profile was performed using peripheral blood from three sepsis patients and three healthy volunteers using microarray screening. The differentially expressed lncRNAs were validated by real-time quantitative polymerase chain reaction (qRT-PCR) in a further set of 22 sepsis patients and 22 healthy volunteers. Among 1316 differentially expressed lncRNAs, 771 were downregulated and 545 were upregulated. Results of the qRT-PCR were consistent with the microarray data. lncRNA ENST00000452391.1, uc001vji.1, and uc021zxw.1 were significantly differentially expressed between sepsis patients and healthy volunteers. Moreover, lncRNA ENST00000504301.1 and ENST00000452391.1 were significantly differentially expressed between sepsis survivors and nonsurvivors. The lncRNA expression profile in the peripheral blood of sepsis patients significantly differed from that of healthy volunteers. Circulating lncRNAs may be good candidates for sepsis biomarkers.

  14. The New Sepsis Definitions: Implications for the Basic and Translational Research Communities.

    Science.gov (United States)

    Coopersmith, Craig M; Deutschman, Clifford S

    2017-03-01

    New definitions of sepsis and septic shock were published in early 2016, updating old definitions that have not been revisited since 2001. These new definitions should profoundly affect sepsis research. In addition, these papers present clinical criteria for identifying infected patients who are highly likely to have or to develop sepsis or septic shock. In contrast to previous approaches, these new clinical criteria are evidence based. In this review, two of the authors of the new definitions detail the content of the papers and explore the implications for shock and sepsis researchers.

  15. Preventing intensive care admissions for sepsis in tropical Africa (PICASTA): an extension of the international pediatric global sepsis initiative: an African perspective.

    Science.gov (United States)

    Pollach, Gregor; Namboya, Felix

    2013-07-01

    The Global Sepsis Initiative recommends prevention of sepsis through immunizations, vitamins, breast feeding, and other important interventions. In our study, we consider a second set of proposals for preventing intensive care admissions for sepsis in tropical Africa, which have been specifically designed to further prevent ICU admissions for sepsis in the group A nation hospital setting. To reduce admissions with severe sepsis in an ICU of a group A nation through the identification of challenges leading to preventable, foreseeable, or nosocomial sepsis specific to our setting. Malawi is one of the poorest countries in the world. Lacking the ability to comply with standard sepsis treatment, we conducted over 4 years several studies, audits, and surveys to identify challenges leading to preventable pediatric sepsis in our setting. We developed a method to identify malnourished children through a "gatekeeper" in the theaters without any equipment, tried to implement the World Health Organization's Safe Surgery Campaign checklist, evaluated our educational courses for the districts to improve the quality of referrals, looked into the extreme fasting times discovered in our hospital, trained different cadres in the districts to deal with peripartal and posttraumatic sepsis, and identified the needs in human resources to deal with pediatric sepsis in our setting. Six foci were identified as promising to work on in future. Focus 1: Preventing elective operations and procedures in malnourished children in the hospital and in the district: 134 of 145 nurses (92.4%) and even 25 of 31 African laymen (80.6%) were able to identify malnourished children with their own fingers. Focus 2: Preventing sepsis-related problems in emergencies through the implementation of the Safe Surgery Campaign checklist: only 100 of 689 forms (14.5%) were filled in due to challenges in ownership, communication responsibility, and time constraints. Focus 3: Preventing sepsis through the reduction

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

    Science.gov (United States)

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

    2014-10-01

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

  17. Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation.

    Science.gov (United States)

    Lupia, E; Bosco, O; Mariano, F; Dondi, A E; Goffi, A; Spatola, T; Cuccurullo, A; Tizzani, P; Brondino, G; Stella, M; Montrucchio, G

    2009-06-01

    Thrombopoietin (TPO) is a humoral growth factor that does not induce platelet aggregation per se, but enhances platelet activation in response to several agonists. Circulating levels of TPO are increased in patients with sepsis and are mainly related to sepsis severity. To investigate the potential contribution of elevated TPO levels in platelet activation during burn injury complicated or not by sepsis. We studied 22 burned patients, 10 without and 12 with sepsis, and 10 healthy subjects. We measured plasma levels of TPO, as well as leukocyte-platelet binding and P-selectin expression. The priming activity of plasma from burned patients or healthy subjects on platelet aggregation and leukocyte-platelet binding, and the role of TPO in these effects were also studied in vitro. Burned patients without and with sepsis showed higher circulating TPO levels and increased monocyte-platelet binding compared with healthy subjects. Moreover, TPO levels, monocyte-platelet binding and P-selectin expression were significantly higher in burned patients with sepsis than in burned patients without sepsis. In vitro, plasma from burned patients without and with sepsis, but not from healthy subjects, primed platelet aggregation, monocyte-platelet binding and platelet P-selectin expression. The effect of plasma from burned patients with sepsis was significantly higher than that of plasma from burned patients without sepsis. An inhibitor of TPO prevented the priming effect of plasma from burned patients. Increased TPO levels may enhance platelet activation during burn injury and sepsis, potentially participating in the pathogenesis of multi-organ failure in these diseases.

  18. A Computable Definition of Sepsis Facilitates Screening and Performance Improvement Tracking.

    Science.gov (United States)

    Alessi, Lauren J; Warmus, Holly R; Schaffner, Erin K; Kantawala, Sajel; Carcillo, Joseph; Rosen, Johanna; Horvat, Christopher M

    2018-03-01

    Sepsis kills almost 5,000 children annually, accounting for 16% of pediatric health care spending in the United States. We sought to identify sepsis within the Electronic Health Record (EHR) of a quaternary children's hospital to characterize disease incidence, improve recognition and response, and track performance metrics. Methods are organized in a plan-do-study-act cycle. During the "plan" phase, electronic definitions of sepsis (blood culture and antibiotic within 24 hours) and septic shock (sepsis plus vasoactive medication) were created to establish benchmark data and track progress with statistical process control. The performance of a screening tool was evaluated in the emergency department. During the "do" phase, a novel inpatient workflow is being piloted, which involves regular sepsis screening by nurses using the tool, and a regimented response to high risk patients. Screening tool use in the emergency department reduced time to antibiotics (Fig. 1). Of the 6,159 admissions, EHR definitions identified 1,433 (23.3%) between July and December 2016 with sepsis, of which 159 (11.1%) had septic shock. Hospital mortality for all sepsis patients was 2.2% and 15.7% for septic shock (Table 1). These findings approximate epidemiologic studies of sepsis and severe sepsis, which report a prevalence range of 0.45-8.2% and mortality range of 8.2-25% (Table 2). 1-5 . Implementation of a sepsis screening tool is associated with improved performance. The prevalence of sepsis conditions identified with electronic definitions approximates the epidemiologic landscape characterized by other point-prevalence and administrative studies, providing face validity to this approach, and proving useful for tracking performance improvement.

  19. Innovative haematological parameters for early diagnosis of sepsis in adult patients admitted in intensive care unit.

    Science.gov (United States)

    Buoro, Sabrina; Manenti, Barbara; Seghezzi, Michela; Dominoni, Paola; Barbui, Tiziano; Ghirardi, Arianna; Carobbio, Alessandra; Marchesi, Gianmariano; Riva, Ivano; Nasi, Alessandra; Ottomano, Cosimo; Lippi, Giuseppe

    2018-04-01

    This study was aimed to investigate the role of erythrocyte, platelet and reticulocyte (RET) parameters, measured by new haematological analyser Sysmex XN and C reactive protein (CRP), for early diagnosis of sepsis during intensive care unit (ICU) stay. The study population consisted of 62 ICU patients, 21 of whom developed sepsis during ICU stay and 41 who did not. The performance for early diagnosing of sepsis was calculated as area under the curve (AUC) of receiver operating characteristics curves analysis. Compared with CRP (AUC 0.81), immature platelet fraction (IPF) (AUC 0.82) showed comparable efficiency for identifying the onset of sepsis. The association with the risk of developing sepsis during ICU stay was also assessed. One day before the onset of sepsis, a decreased of RET% was significantly associated with the risk of developing sepsis (OR=0.35, 95% CI 0.14 to 0.87), whereas an increased of IPF absolute value (IPF#) was significantly associated with the risk of developing sepsis (OR=1.13, 95% CI 1.03 to 1.24) 2 days before the onset of sepsis. The value of CRP was not predictive of sepsis at either time points. IPF# and RET% may provide valuable clinical information for predicting the risk of developing sepsis, thus allowing early management of patients before the onset of clinically evident systemic infections. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    Science.gov (United States)

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. Ureteric stent dwelling time: a risk factor for post-ureteroscopy sepsis.

    Science.gov (United States)

    Nevo, Amihay; Mano, Roy; Baniel, Jack; Lifshitz, David A

    2017-07-01

    To evaluate the association between stent dwelling time and sepsis after ureteroscopy, and identify risk factors for sepsis in this setting. The prospectively collected database of a single institution was queried for all patients who underwent ureteroscopy for stone extraction between 2010 and 2016. Demographic, clinical, preoperative and operative data were collected. The primary study endpoint was sepsis within 48 h of ureteroscopy. Logistic regressions were performed to identify predictors of post-ureteroscopy sepsis in the ureteroscopy cohort and specifically in patients with prior stent insertion. Between October 2010 and April 2016, 1 256 patients underwent ureteroscopy for stone extraction. Risk factors for sepsis included prior stent placement, female gender and Charlson comorbidity index. A total of 601 patients had a ureteric stent inserted before the operation and were included in the study cohort, in which the median age was 56 years, 90 patients were women (30%), and 97 patients were treated for positive preoperative urine cultures (16.1%). Postoperative sepsis, Sepsis rates after stent dwelling times of 1, 2, 3 and >3 months were 1, 4.9, 5.5 and 9.2%, respectively. On multivariate analysis, stent dwelling time, stent insertion because of sepsis, and female gender were significantly associated with post-ureteroscopy sepsis in patients with prior stent placement. Patients who undergo ureteroscopy after ureteric stent insertion have a higher risk of postoperative sepsis. Prolonged stent dwelling time, sepsis as an indication for stent insertion, and female gender are independent risk factors. Stent placement should be considered cautiously, and if inserted, ureteroscopy should be performed within 1 month. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  2. Risk of fever and sepsis evaluations after routine immunizations in the neonatal intensive care unit.

    Science.gov (United States)

    Navar-Boggan, A M; Halsey, N A; Golden, W C; Escobar, G J; Massolo, M; Klein, N P

    2010-09-01

    Premature infants can experience cardiorespiratory events such as apnea after immunization in the neonatal intensive care unit (NICU). These changes in clinical status may precipitate sepsis evaluations. This study evaluated whether sepsis evaluations are increased after immunizations in the NICU. We conducted a retrospective cohort study of infants older than 53 days who were vaccinated in the NICU at the KPMCP (Kaiser Permanente Medical Care Program). Chart reviews were carried out before and after all immunizations were administered and for all sepsis evaluations after age 53 days. The clinical characteristics of infants on the day before receiving a sepsis evaluation were compared between children undergoing post-immunization sepsis evaluations and children undergoing sepsis evaluation at other times. The incidence rate of sepsis evaluations in the post-immunization period was compared with the rate in a control time period not following immunization using Poisson regression. A total of 490 infants met the inclusion criteria. The rate of fever was increased in the 24 h period after vaccination (2.3%, Pimmunization than during the control period, although this was not statistically significant (P=0.09). Infants undergoing a sepsis evaluation after immunization were more likely to have an apneic, bradycardic or moderate-to-severe cardiorespiratory event in the day before the evaluation than were infants undergoing sepsis evaluations at other times (Pimmunization in the NICU, routine vaccination was not associated with increased risk of receiving sepsis evaluations. Providers may be deferring immunizations until infants are clinically stable, or may have a higher threshold for initiating sepsis evaluations after immunization than at other times.

  3. Computerised sepsis protocol management. Description of an early warning system.

    Science.gov (United States)

    de Dios, Begoña; Borges, Marcio; Smith, Timothy D; Del Castillo, Alberto; Socias, Antonia; Gutiérrez, Leticia; Nicolás, Jordi; Lladó, Bartolomé; Roche, Jose A; Díaz, Maria P; Lladó, Yolanda

    2018-02-01

    New strategies need to be developed for the early recognition and rapid response for the management of sepsis. To achieve this purpose, the Multidisciplinary Sepsis Team (MST) developed the Computerised Sepsis Protocol Management (PIMIS). The aim of this study was to evaluate the convenience of using PIMIS, as well as the activity of the MST. An analysis was performed on the data collected from solicited MST consultations (direct activation of PIMIS by attending physician or telephone request) and unsolicited ones (by referral from the microbiology laboratory or an automatic referral via the hospital vital signs recording software [SIDCV]), as well as the hospital department, source of infection, treatment recommendation, and acceptance of this. Of the 1,581 first consultations, 65.1% were solicited consultations (84.1% activation of PIMIS and 15.9% by telephone). The majority of unsolicited consultations were generated by the microbiology laboratory (95.2%), and 4.8% from the SIDCV. Referral from solicited consultations were generated sooner (5.63days vs 8.47days; P<.001) and came from clinical specialties rather than from the surgical ward (73.0% vs 39.1%; P<.001). A recommendation was made for antimicrobial prescription change in 32% of first consultations. The treating physician accepted 78.1% of recommendations. The high rate of solicited consultations and acceptance of recommended prescription changes suggest that a MST is seen as a helpful resource, and that PIMIS software is perceived to be useful and convenient to use, as it is the main source of referral. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  4. A case study in intra-abdominal sepsis.

    Science.gov (United States)

    Paul, Jasmeet S; Ridolfi, Timothy J

    2012-12-01

    Intra-abdominal infections are a common problem for the general surgeon and major sources of morbidity and mortality in the intensive care unit. Some of these patients present with peritonitis that can rapidly progress to septic shock. The basic principles of care include prompt resuscitation, antibiotics, and source control. This article will use a detailed case study to outline the management of a patient with severe intra-abdominal infection from diverticulitis from initial resuscitation to reconstruction. Components of the Surviving Sepsis Campaign as they pertain to surgical patients are discussed and updated, and the concept of damage control general surgery is applied. Copyright © 2012. Published by Elsevier Inc.

  5. Pyomyoma as a Rare Source of Postpartum Sepsis

    Directory of Open Access Journals (Sweden)

    A. DeMaio

    2015-01-01

    Full Text Available Pyomyoma, also known as suppurative leiomyoma, is a rare clinical complication that occurs when a leiomyoma undergoes infarction and subsequent infection. A high index of suspicion is required to make the diagnosis and can be guided by a classic triad of symptoms that includes abdominal pain, sepsis without an obvious source, and a history of leiomyoma. In the vast majority of these cases, total abdominal hysterectomy is required to avoid severe morbidity and potential mortality. We present an unusual case of a postpartum pyomyoma that was successfully treated without the need for hysterectomy. With strong clinical suspicion, early diagnosis, and appropriate management, some affected patients may preserve fertility.

  6. Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care

    NARCIS (Netherlands)

    B.M. van Paridon (Bregje M.); C. Sheppard (Cathy); G.G. Guerra G (Garcia Guerra); A. Joffe (Ari)

    2015-01-01

    textabstractIntroduction: Early administration of antibiotics for sepsis, and of fluid boluses and vasoactive agents for septic shock, is recommended. Evidence for this in children is limited. Methods: The Alberta Sepsis Network prospectively enrolled eligible children admitted to the Pediatric

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  8. Myocardial Injury in Patients With Sepsis and Its Association With Long-Term Outcome

    NARCIS (Netherlands)

    Frencken, Jos F.; Donker, Dirk W; Spitoni, Cristian; Koster-Brouwer, Marlies E; Soliman, Ivo W; Ong, David S Y; Horn, Janneke; van der Poll, Tom; van Klei, Wilton A; Bonten, Marc J M; Cremer, Olaf L.

    BACKGROUND: Sepsis is frequently complicated by the release of cardiac troponin, but the clinical significance of this myocardial injury remains unclear. We studied the associations between troponin release during sepsis and 1-year outcomes. METHODS AND RESULTS: We enrolled consecutive patients with

  9. Unique transcriptomic response to sepsis is observed among patients of different age groups.

    Science.gov (United States)

    Raymond, Steven L; López, María Cecilia; Baker, Henry V; Larson, Shawn D; Efron, Philip A; Sweeney, Timothy E; Khatri, Purvesh; Moldawer, Lyle L; Wynn, James L

    2017-01-01

    Sepsis is a major cause of morbidity and mortality, especially at the extremes of age. To understand the human age-specific transcriptomic response to sepsis, a multi-cohort, pooled analysis was conducted on adults, children, infants, and neonates with and without sepsis. Nine public whole-blood gene expression datasets (636 patients) were employed. Age impacted the transcriptomic host response to sepsis. Gene expression from septic neonates and adults was more dissimilar whereas infants and children were more similar. Neonates showed reductions in inflammatory recognition and signaling pathways compared to all other age groups. Likewise, adults demonstrated decreased pathogen sensing, inflammation, and myeloid cell function, as compared to children. This may help to explain the increased incidence of sepsis-related organ failure and death in adults. The number of dysregulated genes in septic patients was proportional to age and significantly differed among septic adults, children, infants, and neonates. Overall, children manifested a greater transcriptomic intensity to sepsis as compared to the other age groups. The transcriptomic magnitude for adults and neonates was dramatically reduced as compared to children and infants. These findings suggest that the transcriptomic response to sepsis is age-dependent, and diagnostic and therapeutic efforts to identify and treat sepsis will have to consider age as an important variable.

  10. The effect of sepsis and short-term exposure to nitrous oxide on the ...

    African Journals Online (AJOL)

    It is recognised that prolonged anaesthesia with nitrous oxide (N20) induces megaloblastic anaemia by oxidising vitamin B12 To determine whether sepsis aggravates the effect of H20 on haemopoiesis 5 patients with severe sepsis, who required surgery and were exposed to short-term (45 - 105 minutes) N20 anaesthesia, ...

  11. CDC Vital Signs–Think Sepsis. Time Matters.

    Centers for Disease Control (CDC) Podcasts

    2016-08-23

    This podcast 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.

  12. Admission Hyperglycemia in Critically Ill Sepsis Patients: Association With Outcome and Host Response

    NARCIS (Netherlands)

    van Vught, Lonneke A.; Wiewel, Maryse A.; Klein Klouwenberg, Peter M. C.; Hoogendijk, Arie J.; Scicluna, Brendon P.; Ong, David S. Y.; Cremer, Olaf L.; Horn, Janneke; Bonten, Marc M. J.; Schultz, Marcus J.; van der Poll, Tom; de Beer, FrisoM; Bos, LieuweD J.; Frencken, JosF; Glas, GerieJ; van Hooijdonk, RoosmarijnT M.; Huson, Michaë laA M.; Schouten, LauraR A.; Straat, Marleen; Witteveen, Esther; Wieske, Luuk

    2016-01-01

    To investigate whether admission hyperglycemia is associated with the presentation and/or outcome of sepsis, what the influence of hyperglycemia is on key host responses to sepsis, and whether hyperglycemia differentially affects patients with diabetes mellitus. A substudy of a prospective

  13. Non-invasive ventilation in HIV positive patients with sepsis and ...

    African Journals Online (AJOL)

    Method: We conducted an observational prospective cohort study for the NIV arm (in the first half of 2016) with a retrospective chart review for the controls that focused on HIV positive patients with sepsis and hypoxaemic respiratory failure. 77 consecutive HIV positive patients with sepsis and respiratory distress meeting the ...

  14. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients

    DEFF Research Database (Denmark)

    Martí-Carvajal, Arturo J; Solà, Ivan; Gluud, Christian

    2012-01-01

    Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been introduced to reduce the high risk of death associated with severe sepsis or septic shock. This systematic review is an update of a Cochrane review originally published in 2007....

  15. Estrogen protects the liver and intestines against sepsis-induced injury in rats.

    Science.gov (United States)

    Sener, Göksel; Arbak, Serap; Kurtaran, Pelin; Gedik, Nursal; Yeğen, Berrak C

    2005-09-01

    Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-alpha was also assayed in serum samples. In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P Liver function tests and tumor necrosis factor-alpha levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

  16. Epidemiology of Sepsis-like Illness in Young Infants Major Role of Enterovirus and Human Parechovirus

    NARCIS (Netherlands)

    de Jong, Eveline P.; van den Beuken, Monique G. A.; van Elzakker, Erika P. M.; Wolthers, Katja C.; Sprij, Arwen J.; Lopriore, Enrico; Walther, Frans J.; Brus, Frank

    2018-01-01

    Background: Sepsis-like illness is a main cause for hospital admission in young infants. Our aim was to investigate incidence, epidemiology and clinical characteristics of enterovirus (EV) and human parechovirus (HPeV) infections in young infants with sepsis-like illness. Methods: This is a

  17. An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation

    Directory of Open Access Journals (Sweden)

    Olga M. Pena

    2014-11-01

    Interpretation: Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis.

  18. Epidemiology of Adult-population Sepsis in India: A Single Center 5 Year Experience.

    Science.gov (United States)

    Chatterjee, Sharmila; Bhattacharya, Mahuya; Todi, Subhash Kumar

    2017-09-01

    Sepsis is a major worldwide cause of morbidity and mortality. Most sepsis epidemiologic data are from the Western literature. Sparse data from India describe the epidemiology of infection rather than sepsis which is a host response to infection. This study describes the epidemiology of sepsis in the Intensive Care Unit (ICU) of an Indian tertiary care hospital. A prospective study conducted between June 2006 and May 2011. All consecutively admitted patients during the 5 year study >=18 years of age were included and data obtained from hospital in-patient records. Variables measured were the incidence of severe sepsis, ICU, hospital, and 28-day mortality, the median length of ICU stay, median Acute Physiology and Chronic Health Evaluation II (APACHE II) score, infection site, and microbial profile. There were 4711 admissions during the study with 282 (6.2%, 95% confidence interval 2.3, 13.1) admissions with severe sepsis. ICU mortality, hospital mortality, and 28-day mortality were 56%, 63.6%, and 62.8%, respectively. Predominant infection site was respiratory tract. The most common organisms were Gram-negative microbes. The most common microbe was Acinetobacter baumanni. Median APACHE II score on admission was 22 (interquartile range 16-28) and median length of ICU stay was 8 days. Severe sepsis attributable mortality was 85%. Severe sepsis is common in Indian ICUs and is mainly due to Gram-negative organisms. ICU mortality is high in this group and care is resource intensive due to increased length of stay.

  19. Sepsis in Internal Medicine wards: current knowledge, uncertainties and new approaches for management optimization.

    Science.gov (United States)

    Zaccone, Vincenzo; Tosoni, Alberto; Passaro, Giovanna; Vallone, Carla Vincenza; Impagnatiello, Michele; Li Puma, Domenica Donatella; De Cosmo, Salvatore; Landolfi, Raffaele; Mirijello, Antonio

    2017-11-01

    Sepsis represents a global health problem in terms of morbidity, mortality, social and economic costs. Although usually managed in Intensive Care Units, sepsis showed an increased prevalence among Internal Medicine wards in the last decade. This is substantially due to the ageing of population and to multi-morbidity. These characteristics represent both a risk factor for sepsis and a relative contra-indication for the admission to Intensive Care Units. Although there is a lack of literature on the management of sepsis in Internal Medicine, the outcome of these patients seems to be gradually improving. This is due to Internists' increased adherence to guidelines and "bundles". The routine use of SOFA score helps physicians in the definition of septic patients, even if the optimal score has still to come. Point-of-care ultrasonography, lactates, procalcitonin and beta-d-glucan are of help for treatment optimization. The purpose of this narrative review is to focus on the management of sepsis in Internal Medicine departments, particularly on crucial concepts regarding diagnosis, risk assessment and treatment. Key Messages Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The prevalence of sepsis is constantly increasing, affecting more hospital patients than any other disease. At least half of patients affected by sepsis are admitted to Internal Medicine wards. Adherence to guidelines, routine use of clinical and lab scores and point-of-care ultrasonography are of help for early recognition of septic patients and treatment optimization.

  20. Functional impairments at school age of preterm born children with late-onset sepsis

    NARCIS (Netherlands)

    van der Ree, Meike; Tanis, Jozien C.; Van Braeckel, Koenraad N. J. A.; Bos, Arend F.; Roze, Elise

    2011-01-01

    Background: Late-onset sepsis is a relatively common complication particularly of preterm birth that affects approximately a quarter of very low birth weight infants. Aim: We aimed to determine the motor, cognitive, and behavioural outcome at school age of preterm children with late-onset sepsis

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

    Directory of Open Access Journals (Sweden)

    Sajid Shahul

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

  2. Cost and mortality impact of an algorithm-driven sepsis prediction system.

    Science.gov (United States)

    Calvert, Jacob; Hoffman, Jana; Barton, Christopher; Shimabukuro, David; Ries, Michael; Chettipally, Uli; Kerem, Yaniv; Jay, Melissa; Mataraso, Samson; Das, Ritankar

    2017-06-01

    To compute the financial and mortality impact of InSight, an algorithm-driven biomarker, which forecasts the onset of sepsis with minimal use of electronic health record data. This study compares InSight with existing sepsis screening tools and computes the differential life and cost savings associated with its use in the inpatient setting. To do so, mortality reduction is obtained from an increase in the number of sepsis cases correctly identified by InSight. Early sepsis detection by InSight is also associated with a reduction in length-of-stay, from which cost savings are directly computed. InSight identifies more true positive cases of severe sepsis, with fewer false alarms, than comparable methods. For an individual ICU with 50 beds, for example, it is determined that InSight annually saves 75 additional lives and reduces sepsis-related costs by $560,000. InSight performance results are derived from analysis of a single-center cohort. Mortality reduction results rely on a simplified use case, which fixes prediction times at 0, 1, and 2 h before sepsis onset, likely leading to under-estimates of lives saved. The corresponding cost reduction numbers are based on national averages for daily patient length-of-stay cost. InSight has the potential to reduce sepsis-related deaths and to lead to substantial cost savings for healthcare facilities.

  3. Sepsis and development impede muscle protein synthesis in neonatal pigs by different ribosomal mechanisms

    Science.gov (United States)

    In muscle, sepsis reduces protein synthesis (MPS) by restraining translation in neonates and adults. Even though protein accretion decreases with development as neonatal MPS rapidly declines by maturation, the changes imposed by development on the sepsis-associated decrease in MPS have not been desc...

  4. Aetiology of neonatal sepsis at QECH, Blantyre: 1996-2001 | Phiri ...

    African Journals Online (AJOL)

    Neonatal sepsis is common and often fatal in Malawi. The aim of this retrospective study was to report causes, antibiotic resistance and outcome of sepsis in Malawian neonates. We reviewed all blood and cerebrospinal fluid isolates collected between January, 1996, and December, 2001, from inpatients aged 0-30 days ...

  5. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    Directory of Open Access Journals (Sweden)

    Lindsay M Margoles

    Full Text Available Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43 and effector molecules (IFN-γ, TNF as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  6. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    Science.gov (United States)

    Margoles, Lindsay M; Mittal, Rohit; Klingensmith, Nathan J; Lyons, John D; Liang, Zhe; Serbanescu, Mara A; Wagener, Maylene E; Coopersmith, Craig M; Ford, Mandy L

    2016-01-01

    Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  7. Sepsis in general surgery: the 2005-2007 national surgical quality improvement program perspective.

    Science.gov (United States)

    Moore, Laura J; Moore, Frederick A; Todd, S Rob; Jones, Stephen L; Turner, Krista L; Bass, Barbara L

    2010-07-01

    To document the incidence, mortality rate, and risk factors for sepsis and septic shock compared with pulmonary embolism and myocardial infarction in the general-surgery population. Retrospective review. American College of Surgeons National Surgical Quality Improvement Program institutions. General-surgery patients in the 2005-2007 National Surgical Quality Improvement Program data set. Incidence, mortality rate, and risk factors for sepsis and septic shock. Of 363 897 general-surgery patients, sepsis occurred in 8350 (2.3%), septic shock in 5977 (1.6%), pulmonary embolism in 1078 (0.3%), and myocardial infarction in 615 (0.2%). Thirty-day mortality rates for each of the groups were as follows: 5.4% for sepsis, 33.7% for septic shock, 9.1% for pulmonary embolism, and 32.0% for myocardial infarction. The septic-shock group had a greater percentage of patients older than 60 years (no sepsis, 40.2%; sepsis, 51.7%; and septic shock, 70.3%; P surgery resulted in more cases of sepsis (4.5%) and septic shock (4.9%) than did elective surgery (sepsis, 2.0%; septic shock, 1.2%) (P surgery, and the presence of any comorbidity. This study emphasizes the need for early recognition of patients at risk via aggressive screening and the rapid implementation of evidence-based guidelines.

  8. Genetic Factors of the Disease Course After Sepsis: Rare Deleterious Variants Are Predictive

    Directory of Open Access Journals (Sweden)

    Stefan Taudien

    2016-10-01

    Sepsis patients with favorable disease course after sepsis, even in the case of unfavorable preconditions, seem to be affected more often by rare deleterious SNVs in cell signaling and innate immunity related pathways, suggesting a protective role of impairments in these processes against a poor disease course.

  9. Induction of hepatic protein synthesis by a peptide in blood plasma of patients with sepsis and trauma.

    Science.gov (United States)

    Loda, M; Clowes, G H; Dinarello, C A; George, B C; Lane, B; Richardson, W

    1984-08-01

    Accelerated release of amino acids from muscle and their uptake for protein synthesis by liver and other visceral tissues are characteristic of trauma or sepsis. Experimentally, this response is induced by interleukin-1 (IL-1) generated by activated macrophages in vitro. However, IL-1 has not been demonstrated in human blood. A small 4000-dalton peptide recently isolated from plasma of patients with sepsis and trauma induces muscle proteolysis and is called "proteolysis-inducing factor" (PIF). To test whether this agent has the ability also to induce hepatic protein synthesis, a series of animal experiments and clinical observations were undertaken. The structural and secretory (acute-phase reactants) in vitro protein synthesis in livers of normal rats injected intraperitoneally with IL-1 or PIF was significantly greater than that of normal rats or those injected with Ringer's lactate (p less than 0.01). In patients with sepsis and trauma the central plasma clearance rate of amino acids, a measure of visceral (principally hepatic) amino acid uptake, was elevated and correlated with the rates of protein synthesis in incubated liver slices obtained by biopsy at operation from the same patients (p less than 0.05). Both in vivo measured central plasma clearance rate of amino acids and in vitro measured hepatic protein synthesis correlated with plasma levels of PIF in the same patients (p less than 0.01 and p less than 0.05, respectively). We conclude that since PIF, and not IL-1, is present in human plasma and both are produced by activated macrophages, PIF seems to be the stable circulating cleavage product of IL-1, which induces not only muscle proteolysis but also hepatic protein synthesis, principally in the form of acute-phase reactants during infection and other states in which inflammation is present.

  10. Computer versus paper system for recognition and management of sepsis in surgical intensive care.

    Science.gov (United States)

    Croft, Chasen A; Moore, Frederick A; Efron, Philip A; Marker, Peggy S; Gabrielli, Andrea; Westhoff, Lynn S; Lottenberg, Lawrence; Jordan, Janeen; Klink, Victoria; Sailors, R Matthew; McKinley, Bruce A

    2014-02-01

    A system to provide surveillance, diagnosis, and protocolized management of surgical intensive care unit (SICU) sepsis was undertaken as a performance improvement project. A system for sepsis management was implemented for SICU patients using paper followed by a computerized system. The hypothesis was that the computerized system would be associated with improved process and outcomes. A system was designed to provide early recognition and guide patient-specific management of sepsis including (1) modified early warning signs-sepsis recognition score (MEWS-SRS; summative point score of ranges of vital signs, mental status, white blood cell count; after every 4 hours) by bedside nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary tract, soft tissue, other) at bedside by physician or extender; (3) sepsis management protocol (replicable, point-of-care decisions) at bedside by nurse, physician, and extender. The system was implemented first using paper and then a computerized system. Sepsis severity was defined using standard criteria. In January to May 2012, a paper system was used to manage 77 consecutive sepsis encounters (3.9 ± 0.5 cases per week) in 65 patients (77% male; age, 53 ± 2 years). In June to December 2012, a computerized system was used to manage 132 consecutive sepsis encounters (4.4 ± 0.4 cases per week) in 119 patients (63% male; age, 58 ± 2 years). MEWS-SRS elicited 683 site assessments, and 201 had sepsis diagnosis and protocol management. The predominant site of infection was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to occur more using the computerized system (paper, 23%; computer, 35%). Hospital mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with the computerized system. A computerized sepsis management system improves care process and outcome. Early sepsis is recognized and managed with greater frequency compared with severe sepsis or septic shock. The system

  11. Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

    International Nuclear Information System (INIS)

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

    1987-01-01

    The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletal sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement

  12. Expression of NK cell and monocyte receptors in critically ill patients - potential biomarkers of sepsis

    DEFF Research Database (Denmark)

    Kjaergaard, A G; Nielsen, Jeppe Sylvest; Tønnesen, Else

    2015-01-01

    UNLABELLED: Sepsis is characterized by activation of both the innate and adaptive immune systems as a response to infection. During sepsis, the expression of surface receptors expressed on immune competent cells, such as NKG2D and NKp30 on NK cells and TLR4 and CD14 on monocytes, is partly...... regulated by pro- and anti-inflammatory mediators. In this observational study, we aimed to explore whether the expression of these receptors could be used as diagnostic and/or prognostic biomarkers in sepsis. Patients with severe sepsis or septic shock (n = 21) were compared with critically ill non...... were higher in the septic patients compared with the non-septic patients (P sepsis...

  13. Sepsis Patients Display a Reduced Capacity to Activate Nuclear Factor-κB in Multiple Cell Types

    NARCIS (Netherlands)

    Hoogendijk, Arie J.; Garcia-Laorden, M. Isabel; van Vught, Lonneke A.; Wiewel, Maryse A.; Belkasim-Bohoudi, Hakima; Duitman, Janwillem; Horn, Janneke; Schultz, Marcus J.; Scicluna, Brendon P.; van 't Veer, Cornelis; de Vos, Alex F.; van der Poll, Tom

    2017-01-01

    Sepsis is a complex clinical condition associated with high morbidity and mortality. A distinctive feature of sepsis is the reduced capacity of leukocytes to release proinflammatory cytokines in response to ex vivo stimulation. Cellular signaling events leading to immunosuppression in sepsis are not

  14. Gene Network for Identifying the Entropy Changes of Different Modules in Pediatric Sepsis

    Directory of Open Access Journals (Sweden)

    Jing Yang

    2016-12-01

    Full Text Available Background/Aims: Pediatric sepsis is a disease that threatens life of children. The incidence of pediatric sepsis is higher in developing countries due to various reasons, such as insufficient immunization and nutrition, water and air pollution, etc. Exploring the potential genes via different methods is of significance for the prevention and treatment of pediatric sepsis. This study aimed to identify potential genes associated with pediatric sepsis utilizing analysis of gene network and entropy. Methods: The mRNA expression in the blood samples collected from 20 septic children and 30 healthy controls was quantified by using Affymetrix HG-U133A microarray. Two condition-specific protein-protein interaction networks (PINs, one for the healthy control and the other one for the children with sepsis, were deduced by combining the fundamental human PINs with gene expression profiles in the two phenotypes. Subsequently, distinct modules from the two conditional networks were extracted by adopting a maximal clique-merging approach. Delta entropy (ΔS was calculated between sepsis and control modules. Results: Then, key genes displaying changes in gene composition were identified by matching the control and sepsis modules. Two objective modules were obtained, in which ribosomal protein RPL4 and RPL9 as well as TOP2A were probably considered as the key genes differentiating sepsis from healthy controls. Conclusion: According to previous reports and this work, TOP2A is the potential gene therapy target for pediatric sepsis. The relationship between pediatric sepsis and RPL4 and RPL9 needs further investigation.

  15. Contemporary Trends of Reported Sepsis Among Maternal Decedents in Texas: A Population-Based Study.

    Science.gov (United States)

    Oud, Lavi

    2015-09-01

    Recent studies indicate that death certificate-based single-cause-of-death diagnoses can substantially underestimate the contribution of sepsis to mortality in the general population and among maternal decedents. There are no population-based data in the United States on the patterns of the contribution of sepsis to pregnancy-associated deaths. We studied the Texas Inpatient Public Use Data File to identify pregnancy-associated hospitalizations with reported hospital death during 2001-2010. We then examined the annual reporting of sepsis, and that of other reported most common causes of maternal death, including hemorrhage, embolism, preeclampsia/eclampsia, cardiovascular conditions, cardiomyopathy, cerebrovascular accidents, and anesthesia complications. The annual rate of sepsis among decedents, its trend over time, and changes of its annual rank among other examined potential causes of maternal death were assessed. There were 557 pregnancy-associated hospital deaths during study period. Sepsis was reported in 131 (23.5%) decedents. Sepsis has been increasingly reported among decedents, rising by 9.1%/year (P = 0.0025). The rank of sepsis, as compared to the other examined potential causes of maternal death rose from the 5th in 2001 to 1st since 2008. At the end of the last decade, sepsis has been reported in 28.1% of pregnancy-associated deaths. More than one potential cause of maternal death was reported in 39% of decedents. Sepsis has become the most commonly reported potential cause of death among maternal decedents in the present cohort, noted in over 1 in 4 fatal hospitalizations by the end of the last decade. Although causality cannot be inferred from administrative data, given its known contribution to maternal death, it is likely that sepsis plays an increasing role in fatal maternal hospital outcomes. The prevalent co-reporting of multiple potential causes of maternal death in the present cohort underscores the complexity of determining the sources of

  16. Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

    Science.gov (United States)

    Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

    2017-06-01

    Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

  17. Role of presepsin for the evaluation of sepsis in the emergency department.

    Science.gov (United States)

    Pizzolato, Elisa; Ulla, Marco; Galluzzo, Claudia; Lucchiari, Manuela; Manetta, Tilde; Lupia, Enrico; Mengozzi, Giulio; Battista, Stefania

    2014-10-01

    Sepsis, severe sepsis and septic shock are among the most common conditions handled in the emergency department (ED). According to new Sepsis Guidelines, early diagnosis and treatment are the keys to improve survival. Plasma C-reactive protein (CRP) and procalcitonin (PCT) levels, when associated with documented or suspected infection, are now part of the definitions of sepsis. Blood culture is the gold standard method for detecting microorganisms but it requires too much time for results to be known. Sensitive biomarkers are required for early diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. In recent years PCT has been widely used for sepsis differential diagnosis, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. In this mini review we mainly focused on presepsin: we evaluate its diagnostic and prognostic roles in patients presenting to the ED with systemic inflammatory response syndrome (SIRS), suspected sepsis or septic shock.

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

    Directory of Open Access Journals (Sweden)

    Mohammod Jobayer Chisti

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

  19. Effects of paraoxonase, arylesterase, ceruloplasmin, catalase, and myeloperoxidase activities on prognosis in pediatric patients with sepsis.

    Science.gov (United States)

    Ayar, Ganime; Atmaca, Yasemin Men; Alışık, Murat; Erel, Özcan

    2017-05-01

    The present study aimed to investigate the levels of paraoxonase (PON), stimulated paraoxonase (SPON), arylesterase (ARE), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase (CAT) in pediatric sepsis and to explore their effects on the prognosis of sepsis. Patients diagnosed with sepsis (n=33) and healthy controls (n=30) were included. PON, SPON, ARE, CLP, MPO, and CAT activities were measured in the sepsis and control groups. Additionally, the parameters were compared between survivors and non-survivors in the sepsis group. The levels of hemoglobin, white blood cell, platelet, lactate, and C-reactive protein were measured in the blood samples drawn from the patients with sepsis at diagnosis, at the 48th hour, and on day 7. The pediatric risk of mortality and pediatric logistic organ dysfunction scores of the patients were used for the estimation of severity of disease. Lower ARE (153.24 vs. 264.32U/L; p<0.001), lower CLP (80.58 vs. 97.98U/L; p=0.032), lower MPO (91.24 vs. 116.55U/L; p=0.023), and higher CAT levels (256.5 vs.145.5kU/L; p=0.003) were determined in the sepsis group as compared to the control group. There was no difference between the groups in terms of PON or SPON levels. No difference was determined between the survivors and non-survivors in terms of any of the parameters. The present study determined that ARE, CLP, CAT, and MPO levels are different between the pediatric patients with sepsis and healthy controls. ARE level can be a potent biomarker for sepsis in critical patients in intensive care units. Further studies with larger samples are required to demonstrate the value of these parameters as prognostic biomarkers in pediatric sepsis. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  20. Symptoms of depression in survivors of severe sepsis: a prospective cohort study of older Americans.

    Science.gov (United States)

    Davydow, Dimitry S; Hough, Catherine L; Langa, Kenneth M; Iwashyna, Theodore J

    2013-09-01

    To examine if incident severe sepsis is associated with increased risk of subsequent depressive symptoms and to assess which patient characteristics are associated with increased risk of depressive symptoms. Prospective longitudinal cohort study. Population-based cohort of older U.S. adults interviewed as part of the Health and Retirement Study (1998-2006). A total of 439 patients who survived 471 hospitalizations for severe sepsis and completed at least one follow-up interview. Depressive symptoms were assessed with a modified version of the Center for Epidemiologic Studies Depression Scale. Severe sepsis was identified using a validated algorithm in Medicare claims. The point prevalence of substantial depressive symptoms was 28% at a median of 1.2 years before sepsis, and remained 28% at a median of 0.9 years after sepsis. Neither incident severe sepsis (relative risk [RR]: 1.00; 95% confidence interval [CI]: 0.73, 1.34) nor severe sepsis-related clinical characteristics were significantly associated with subsequent depressive symptoms. These results were robust to potential threats from missing data or alternative outcome definitions. After adjustment, presepsis substantial depressive symptoms (RR: 2.20; 95% CI: 1.66, 2.90) and worse postsepsis functional impairment (RR: 1.08 per new limitation; 95% CI: 1.03, 1.13) were independently associated with substantial depressive symptoms after sepsis. The prevalence of substantial depressive symptoms in severe sepsis survivors is high but is not increased relative to their presepsis levels. Identifying this large subset of severe sepsis survivors at increased risk for major depression, and beginning interventions before hospital discharge, may improve outcomes. Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Psychosocial stress as a risk factor for sepsis: a population-based cohort study.

    Science.gov (United States)

    Ojard, Connor; Donnelly, John P; Safford, Monika M; Griffin, Russell; Wang, Henry E

    2015-01-01

    To characterize the relationship between stress and future risk of sepsis. We also evaluated the role of depression in this relationship. We used population-based data on 30,183 participants in the Reasons for Geographic and Racial Differences in Stroke cohort, characterizing stress using the Perceived Stress Scale (PSS) and depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D). We identified incident sepsis events as hospitalizations for a serious infection with the presence of at least two systemic inflammatory response syndrome criteria. We assessed associations between PSS and incidence of sepsis for 1 and 10 years of follow-up, adjusting for demographics and chronic medical conditions and assessing the role of health behaviors and CES-D in these relationships. In 2003 to 2012, 1500 participants experienced an episode of sepsis. Mean PSS and CES-D scores were 3.2 (2.9) and 1.2 (2.1). PSS was associated with increased 1-year adjusted incidence of sepsis (hazard ratio [HR] = 1.21 per PSS standard deviation, 95% confidence interval = 1.06-1.38); multivariable adjustment for health behaviors and CES-D did not change this association (1.20, 1.03-1.39). PSS was also associated with increased 10-year adjusted incidence of sepsis (HR = 1.07 per PSS standard deviation; 95% confidence interval = 1.02-1.13). Multivariable adjustment showed that health behaviors did not affect this long-term association, whereas the addition of CES-D reduced the association between PSS and sepsis during 10-year follow-up (HR = 1.04, 0.98-1.11). Increased stress was associated with higher 1-year adjusted incidence of sepsis, even after accounting for depressive symptoms. The association between stress and 10-year adjusted incidence of sepsis was also significant, but this association was reduced when adjusting for depressive symptoms. Reduction of stress may limit short-term sepsis risk.

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

    Directory of Open Access Journals (Sweden)

    Ding Wang

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

  3. The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients.

    Science.gov (United States)

    Sterling, Sarah A; Puskarich, Michael A; Glass, Andrew F; Guirgis, Faheem; Jones, Alan E

    2017-09-01

    The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. Secondary analysis of two clinical trials of early septic shock resuscitation. Large academic emergency departments in the United States. Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006). In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.

  4. Improved Early Detection of Sepsis in the ED With a Novel Monocyte Distribution Width Biomarker.

    Science.gov (United States)

    Crouser, Elliott D; Parrillo, Joseph E; Seymour, Christopher; Angus, Derek C; Bicking, Keri; Tejidor, Liliana; Magari, Robert; Careaga, Diana; Williams, JoAnna; Closser, Douglas R; Samoszuk, Michael; Herren, Luke; Robart, Emily; Chaves, Fernando

    2017-09-01

    Sepsis most often presents to the ED, and delayed detection is harmful. WBC count is often used to detect sepsis, but changes in WBC count size also correspond to sepsis. We sought to determine if volume increases of circulating immune cells add value to the WBC count for early sepsis detection in the ED. A blinded, prospective cohort study was conducted in two different ED populations within a large academic hospital. Neutrophil and monocyte volume parameters were measured in conjunction with routine CBC testing on a UniCel DxH 800 analyzer at the time of ED admission and were evaluated for the detection of sepsis. There were 1,320 subjects in the ED consecutively enrolled and categorized as control subjects (n = 879) and those with systemic inflammatory response syndrome (SIRS) (n = 203), infection (n = 140), or sepsis (n = 98). Compared with other parameters, monocyte distribution width (MDW) best discriminated sepsis from all other conditions (area under the curve [AUC], 0.79; 95% CI, 0.73-0.84; sensitivity, 0.77; specificity, 0.73; MDW threshold, 20.50), sepsis from SIRS (AUC, 0.74; 95% CI, 0.67-0.84), and severe sepsis from noninfected patients in the ED (AUC, 0.88; 95% CI, 0.75-0.99; negative predictive value, 99%). The added value of MDW to WBC count was statistically significant (AUC, 0.89 for MDW + WBC vs 0.81 for WBC alone; P sepsis compared with WBC count alone at the time of admission in the ED. ClinicalTrials.gov; No.: NCT02232750; URL: www.clinicaltrials.gov. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  5. S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis.

    Science.gov (United States)

    Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing

    2017-12-15

    Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.

  6. Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis.

    Science.gov (United States)

    Kumar, S; Gupta, E; Kaushik, S; Kumar Srivastava, V; Mehta, S K; Jyoti, A

    2018-04-01

    Sepsis is a condition caused by infection followed by unregulated inflammatory response which may lead to the organ dysfunction. During such condition, over-production of oxidants is one of the factors which contribute cellular toxicity and ultimately organ failure and mortality. Antioxidants having free radicals scavenging activity exert protective role in various diseases. This study has been designed to evaluate the levels of oxidative and antioxidative activity in sepsis patients and their correlation with the severity of the sepsis. A total of 100 sepsis patients and 50 healthy controls subjects were enrolled in this study from the period October 2016 to June 2017. The investigation included measurements of oxidative enzyme, myeloperoxidase (MPO), antioxidant enzymes including superoxide dismutase activity (SOD) and catalase activity (CAT) and cytokines (TNF-α, IL-8 and IFN-γ). Furthermore, the level of these activities was correlated with severity of sepsis. Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects). Cytokines were also found to be increased in sepsis patients. However, plasma SOD and CAT activities were significantly attenuated (P sepsis patients compared with controls subjects. Moreover, inverse relation between antioxidant enzymes (SOD and CAT) and organ failure assessment (SOFA), physiological score (APACHE II), organ toxicity specific markers have been observed as demonstrated by Pearson's correlation coefficient. This study suggests that imbalance between oxidant and antioxidant plays key role in the severity of sepsis. © 2018 The Foundation for the Scandinavian Journal of Immunology.

  7. Severe malaria vivax with sepsis bacterial: a case report

    Science.gov (United States)

    Tarigan, P.; Ginting, F.

    2018-03-01

    Malaria cases are often misdiagnosis by clinicians in tropical areas like Indonesia. Some cases show overlapping signs and symptoms of another infection that are common in the tropical areas such as typhoid, dengue, and leptospirosis. It can be misdiagnosed in practice and led to a wrong management that can end fatally. Severe malaria is usually caused by Plasmodium falciparum. P. vivax can also cause severe malaria but the cases reported are uncommon. Since infections with severe P. vivax that generally results in serious disease is quite uncommon in Indonesia, their identification and management are important. We report a case of severe malaria with sepsis, renal injury and hepatic impairment associated with malaria in a 70-year-old male. Clinical manifestations included anemia, sepsis, and elevated serum creatinine, urea, total bilirubin, and procalcitonin. The rapid diagnostic test for malaria and microscopic examination of blood smears were positive for P. vivax. The patient was treated as severe malaria with intravenous artesunate for six days, followed by oral treatment of primaquine for 14 days. Intravenous fluid therapy, antipyretic, anti-malaria and antibiotic treatment were administered. The patient was stable and then discharged from the hospital. The prognosis depends much on early diagnosis and appropriate supportive treatment.

  8. Petechial Hemorrhage: A clinical diagnosis of neonatal Thrombocytopenia and sepsis

    Directory of Open Access Journals (Sweden)

    Deepak Kumar sharma

    2015-02-01

    Full Text Available A preterm female baby with birth weight of 1.5kg was referred to our hospital on day 6 for difficulty in breathing. Baby was admitted at birth for respiratory distress and feed intolerance to other hospital and in view of clinical deterioration baby was referred. Baby had thrombocytopenia with platelets counts of 11000/ mm3 and high CRP titer. Baby had petechial haemorrhagic spots all over the body with hepatosplenomegaly and sclerema (figure 1,2,3. Baby further platelets counts were 3000, 43000, 67000 and then normal. Baby was managed with antibiotics and platelets transfusion. Gradually baby counts improved and petechial spots disappeared. Discussion Neonatal Sepsis is a common complication in the neonatal intensive care unit. It is most common in the smallest and most premature infants in whom the clinical presentation can be subtle and nonspecific. Thrombocytopenia is the common manifestation of neonatal sepsis in sick babies(1. The manifestation can be seen in newborn as petechial spots over the body with predominance over chest and abdomen(2.Thrombocytopenia is seen in 18% to 35% of NICU patients, and in 73% of extremely low birth weight (ELBW infants(3. Bacterial,fungal and viral infection causes thrombocytopenia. Infection causes damage to vascular endothelium which increases the destruction of platelets and there removal by reticuloendothelial system(4

  9. Heparin defends against the toxicity of circulating histones in sepsis.

    Science.gov (United States)

    Wang, Feifei; Zhang, Naipu; Li, Biru; Liu, Lanbo; Ding, Lei; Wang, Ying; Zhu, Yimin; Mo, Xi; Cao, Qing

    2015-06-01

    Although circulating histones were demonstrated as major mediators of death in septic mice models, their roles in septic patients are not clarified. The present study sought to evaluate the clinical relevance of the circulating histone levels in septic children, and the antagonizing effects of heparin on circulating histones. Histone levels in the plasma of septic children were significantly higher than healthy controls, and positively correlated with disease severity. Histone treatment could activate NF-κB pathway of the endothelial cells and induce the secretion of large amount of cytokines that further amplify inflammation, subsequently leading to organ damage. Co-injection of low dose heparin with lethal dose histones could protect mouse from organ damage and death by antagonizing circulating histones, and similar effects were also observed in other septic models. Collectively, these findings indicated that circulating histones might serve as key factors in the pathogenesis of sepsis and their levels in plasma might be a marker for disease progression and prognosis. Furthermore, low dose heparin might be an effective therapy to hamper sepsis progression and reduce the mortality.

  10. Percutaneous biliary drainage in acute suppurative cholangitis with biliary sepsis

    International Nuclear Information System (INIS)

    Kim, Hyung Lyul; Cho, June Sik; Kwon, Soon Tae; Lee, Sang Jin; Rhee, Byung Chull

    1993-01-01

    Acute suppurative cholangitis is a severe inflammatory process of the bile duct occurred as result of partial or complete obstruction of the bile duct, and may manifest clinically severe form of disease, rapidly deteriorating to life-threatening condition. We analyzed emergency percutaneous transhepatic biliary drainage in 20 patients of acute suppurative cholangitis with biliary sepsis to evaluate the therapeutic effect and complication of the procedure. The underlying cause were 12 benign disease(stones) and eight malignant tumors and among eight malignant tumors, bile duct stones(n=4) and clonorchiasis(n=1) were combined. Percutaneous transhepatic biliary drainage was performed successfully in 17 of 20 patients resulting in improvement of general condition and failed in three patients. The procedure were preterminated due to the patient's condition in two and biliary-proto fistula was developed in one. After biliary decompression by percutaneous transhepatic biliary drainage, effective and successful elective surgery was performed in nine cases, which were seven biliary stones and two biliary cancer with stones. Our experience suggest that emergency percutaneous transhepatic biliary drainage is an initial and effective treatment of choice for acute suppurative cholangitis with sepsis and a safe alternative for nonsurgical treatment

  11. Paramedic-Initiated CMS Sepsis Core Measure Bundle Prior to Hospital Arrival: A Stepwise Approach.

    Science.gov (United States)

    Walchok, Jason G; Pirrallo, Ronald G; Furmanek, Douglas; Lutz, Martin; Shope, Colt; Giles, Brandi; Gue, Greta; Dix, Aaron

    2017-01-01

    To improve patient outcomes, the Center for Medicare and Medicaid Services (CMS) implemented core measures that outline the initial treatment of the septic patient. These measures include initial blood culture collection prior to antibiotics, adequate intravenous fluid resuscitation, and early administration of broad spectrum antibiotics. We sought to determine if Paramedics can initiate the CMS sepsis core measure bundle in the prehospital field reliably. This is a retrospective, case series from a 3rd service EMS system model in Greenville, South Carolina between November 17, 2014 and February 20, 2016. An adult Prehospital Sepsis Assessment Tool was created using the 2012 Surviving Sepsis guidelines: 2 of 3 signs of systemic inflammatory response (heart rate, respiratory rate, oral temperature) and a known or suspected source of infection. A "Sepsis Alert" was called by paramedics and upon IV access a set of blood cultures and blood for lactate analysis was collected prior to field antibiotic administration. The Sepsis Alert was compared to serum lactate levels and ICD 9 or 10 admitting diagnosis of Sepsis, Severe Sepsis, or Septic Shock. Blood culture contamination, serum lactate, and antibiotic match were determined by in-hospital laboratory analysis. A total of 120 trained paramedics called 1,185 "Sepsis Alerts" on 56,643 patients (50.3% Male, mean age 70). Patients with missing discharge diagnosis were eliminated (n = 31). The admitting diagnosis of sepsis overall was 73.5% (848/1154): Sepsis 50% (578/1154), Severe Sepsis 14.6% (169/1154), Septic Shock 8.9% (101/1154). A total of 946 blood cultures were collected in the prehospital setting, with a 95.04% (899/946) no contamination rate. Contamination was found in 4.96% (47/946). A total of 179 (18.9%) of the uncontaminated blood cultures were found to have positive growth with 720 (76.1%) having no growth. EMS administered antibiotics matched blood culture positive growth in 72% of patients. The lactate

  12. Modulation of myocardial mitochondrial mechanisms during severe polymicrobial sepsis in the rat.

    Directory of Open Access Journals (Sweden)

    Mani Chopra

    Full Text Available We tested the hypothesis that 5-Hydroxydecanoic acid (5HD, a putative mitoK(ATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival.Male Sprague-Dawley rats (350-400 g were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1, Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles in the presence/absence of 5HD (100 µmoles. A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (-40% and at 6 hr post-sepsis (-20%. Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group. The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C.The data suggest that Bax activation is an upstream event that may precede the opening of the mitoK(ATP channels in sepsis. We concluded that mitoK(ATP channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction.

  13. Modulation of myocardial mitochondrial mechanisms during severe polymicrobial sepsis in the rat.

    Science.gov (United States)

    Chopra, Mani; Golden, Honey B; Mullapudi, Srinivas; Dowhan, William; Dostal, David E; Sharma, Avadhesh C

    2011-01-01

    We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoK(ATP) channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Male Sprague-Dawley rats (350-400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD (100 µmoles). A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (-40%) and at 6 hr post-sepsis (-20%). Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group) and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group). The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C. The data suggest that Bax activation is an upstream event that may precede the opening of the mitoK(ATP) channels in sepsis. We concluded that mitoK(ATP) channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction.

  14. Physiopathology, importance and usefulness of lactate in patients with sepsis Fisiopatología, importancia y utilidad del lactato en pacientes con sepsis*

    Directory of Open Access Journals (Sweden)

    Maycos Leandro Zapata Muñoz

    2010-08-01

    Full Text Available

    Worldwide, sepsis is acknowledged as a significant cause of hospital-associated mortality. There is an increasing interest in identifying the group of patients that can benefit more from an early and aggressive therapy. Lactate is an important cellular metabolite, traditionally interpreted as a marker of low oxygen delivery to tissues during sepsis. Given recent investigations about the physiology of lactate production, and with the understanding of sepsis as a systemic response, interpretation of a high lactate level may include various processes, not all of them harmful. In this review, the different cellular processes that may explain high lactate levels in sepsis are described. Its current clinical usefulness and proposals for future interpretation in the reanimation of patients with sepsis are analyzed.

    La sepsis como causante de alta mortalidad en instituciones hospitalarias es un evento reconocido mundialmente. Existe un interés creciente en identificar el grupo de pacientes que más se pueda beneficiar de una terapia temprana e intensiva. El lactato es un marcador importante de los procesos metabólicos celulares, y en sepsis se lo ha interpretado como un biomarcador que indica la deficiencia de aporte de oxígeno a los tejidos. Si se tienen en cuenta investigaciones recientes sobre la fisiología de la producción de lactato, y se entiende

  15. Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or Sepsis.

    Science.gov (United States)

    Matthay, Michael A; Pati, Shibani; Lee, Jae-Woo

    2017-02-01

    Several experimental studies have provided evidence that bone-marrow derived mesenchymal stem (stromal) cells (MSC) may be effective in treating critically ill surgical patients who develop traumatic brain injury, acute renal failure, or the acute respiratory distress syndrome. There is also preclinical evidence that MSC may be effective in treating sepsis-induced organ failure, including evidence that MSC have antimicrobial properties. This review considers preclinical studies with direct relevance to organ failure following trauma, sepsis or major infections that apply to critically ill patients. Progress has been made in understanding the mechanisms of benefit, including MSC release of paracrine factors, transfer of mitochondria, and elaboration of exosomes and microvesicles. Regardless of how well they are designed, preclinical studies have limitations in modeling the complexity of clinical syndromes, especially in patients who are critically ill. In order to facilitate translation of the preclinical studies of MSC to critically ill patients, there will need to be more standardization regarding MSC production with a focus on culture methods and cell characterization. Finally, well designed clinical trials will be needed in critically ill patient to assess safety and efficacy. Stem Cells 2017;35:316-324. © 2016 AlphaMed Press.

  16. Postnatal Age Is a Critical Determinant of the Neonatal Host Response to Sepsis

    Science.gov (United States)

    Wynn, James L; Guthrie, Scott O; Wong, Hector R; Lahni, Patrick; Ungaro, Ricardo; Lopez, M Cecilia; Baker, Henry V; Moldawer, Lyle L

    2015-01-01

    Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often-protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 h after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively on the basis of clinical exam and laboratory results over the next 72 h from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 d, or late, ≥3 d). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on postnatal age. PMID:26052715

  17. Muscle Mass Depletion Associated with Poor Outcome of Sepsis in the Emergency Department.

    Science.gov (United States)

    Lee, YoonJe; Park, Hyun Kyung; Kim, Won Young; Kim, Myung Chun; Jung, Woong; Ko, Byuk Sung

    2018-05-08

    Muscle mass depletion has been suggested to predict morbidity and mortality in various diseases. However, it is not well known whether muscle mass depletion is associated with poor outcome in sepsis. We hypothesized that muscle mass depletion is associated with poor outcome in sepsis. Retrospective observational study was conducted in an emergency department during a 9-year period. Medical records of 627 patients with sepsis were reviewed. We divided the patients into 2 groups according to 28-day mortality and compared the presence of muscle mass depletion assessed by the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on abdomen CT scans. Univariate and multivariate logistic regression analyses were conducted to examine the association of scarcopenia on the outcome of sepsis. A total of 274 patients with sepsis were finally included in the study: 45 (16.4%) did not survive on 28 days and 77 patients (28.1%) were identified as having muscle mass depletion. The presence of muscle mass depletion was independently associated with 28-day mortality on multivariate logistic analysis (OR 2.79; 95% CI 1.35-5.74, p = 0.01). Muscle mass depletion evaluated by CT scan was associated with poor outcome of sepsis patients. Further studies on the appropriateness of specific treatment for muscle mass depletion with sepsis are needed. © 2018 S. Karger AG, Basel.

  18. Automated Detection of Sepsis Using Electronic Medical Record Data: A Systematic Review.

    Science.gov (United States)

    Despins, Laurel A

    Severe sepsis and septic shock are global issues with high mortality rates. Early recognition and intervention are essential to optimize patient outcomes. Automated detection using electronic medical record (EMR) data can assist this process. This review describes automated sepsis detection using EMR data. PubMed retrieved publications between January 1, 2005 and January 31, 2015. Thirteen studies met study criteria: described an automated detection approach with the potential to detect sepsis or sepsis-related deterioration in real or near-real time; focused on emergency department and hospitalized neonatal, pediatric, or adult patients; and provided performance measures or results indicating the impact of automated sepsis detection. Detection algorithms incorporated systemic inflammatory response and organ dysfunction criteria. Systems in nine studies generated study or care team alerts. Care team alerts did not consistently lead to earlier interventions. Earlier interventions did not consistently translate to improved patient outcomes. Performance measures were inconsistent. Automated sepsis detection is potentially a means to enable early sepsis-related therapy but current performance variability highlights the need for further research.

  19. Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations

    Directory of Open Access Journals (Sweden)

    M. Neri

    2016-01-01

    Full Text Available Background. Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients. Aim. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis. Conclusions. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

  20. Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

    Science.gov (United States)

    Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

    2017-10-01

    Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Soluble Triggering Receptor Expressed on Myeloid Cells-1 as a Novel Marker for Abdominal Sepsis.

    Science.gov (United States)

    Song, Xiaofei; Song, Yucheng; Zhang, Xuedong; Xue, Huanzhou

    2017-07-01

    The aim of the study was to investigate the concentration and diagnostic significance of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in acute abdominal conditions. Plasma specimens were obtained from 68 patients with abdominal sepsis, 60 patients with systemic inflammatory response syndrome (SIRS), and 60 healthy individuals. The sepsis group was divided into the survival and death groups according to the 28-d outcome. Plasma sTREM-1, procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count were measured. A receiver operating characteristic curve (ROC) was used to compare the diagnostic values of sTREM-1, PCT, CRP, and WBC count. In addition, the correlation between plasma sTREM-1 and the Acute Physiology and Chronic Health Evaluation (APACHE) II score in the sepsis group was assessed by Spearman correlation analysis. The plasma concentration of sTREM-1 in the sepsis group was significantly higher than that in the SIRS and healthy groups (both p sepsis vs. SIRS showed that the area under the curve of sTREM-1 (0.82) was greater than that of PCT (0.77), CRP (0.72), and WBC count (0.70). Additionally, in the sepsis group, the plasma sTREM-1 concentration correlated positively with the APACHE II score (r = 0.41; p sepsis.

  2. Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis.

    Science.gov (United States)

    Motzkus, Christine A; Luckmann, Roger

    2017-09-01

    Sepsis treatment protocols emphasize source control with empiric antibiotics and fluid resuscitation. Previous reviews have examined the impact of infection site and specific pathogens on mortality from sepsis; however, no recent review has addressed the infection site. This review focuses on the impact of infection site on hospital mortality among patients with sepsis. The PubMed database was searched for articles from 2001 to 2014. Studies were eligible if they included (1) one or more statistical models with hospital mortality as the outcome and considered infection site for inclusion in the model and (2) adult patients with sepsis, severe sepsis, or septic shock. Data abstracted included stage of sepsis, infection site, and raw and adjusted effect estimates. Nineteen studies were included. Infection sites most studied included respiratory (n = 19), abdominal (n = 19), genitourinary (n = 18), and skin and soft tissue infections (n = 11). Several studies found a statistically significant lower mortality risk for genitourinary infections on hospital mortality when compared to respiratory infections. Based on studies included in this review, the impact of infection site in patients with sepsis on hospital mortality could not be reliably estimated. Misclassification among infections and disease states remains a serious possibility in studies on this topic.

  3. Determinants of Carboxyhemoglobin Levels and Relationship with Sepsis in a Retrospective Cohort of Preterm Neonates.

    Directory of Open Access Journals (Sweden)

    Andrew J McArdle

    Full Text Available Carboxyhemoglobin levels in blood reflect endogenous carbon monoxide production and are often measured during routine blood gas analysis. Endogenous carbon monoxide production has been reported to be increased during sepsis, but carboxyhemoglobin levels have not been thoroughly evaluated as a biomarker of sepsis. We sought to determine whether carboxyhemoglobin levels were elevated during sepsis in a high risk population of premature neonates. We conducted a retrospective cohort study of 30 infants in two neonatal intensive care units using electronic medical and laboratory records. The majority of infants were extremely premature and extremely low birth weight, and 25 had at least one episode of sepsis. We collected all carboxyhemoglobin measurements during their in-patient stay and examined the relationship between carboxyhemoglobin and a variety of clinical and laboratory parameters, in addition to the presence or absence of sepsis, using linear mixed-effect models. We found that postnatal age had the most significant effect on carboxyhemoglobin levels, and other significant associations were identified with gestational age, hemoglobin concentration, oxyhemoglobin saturation, and blood pH. Accounting for these covariates, there was no significant relationship between the onset of sepsis and carboxyhemoglobin levels. Our results show that carboxyhemoglobin is unlikely to be a clinically useful biomarker of sepsis in premature infants, and raise a note of caution about factors which may confound the use of carbon monoxide as a clinical biomarker for other disease processes such as hemolysis.

  4. Determinants of Carboxyhemoglobin Levels and Relationship with Sepsis in a Retrospective Cohort of Preterm Neonates.

    Science.gov (United States)

    McArdle, Andrew J; Webbe, James; Sim, Kathleen; Parrish, Graham; Hoggart, Clive; Wang, Yifei; Kroll, J Simon; Godambe, Sunit; Cunnington, Aubrey J

    2016-01-01

    Carboxyhemoglobin levels in blood reflect endogenous carbon monoxide production and are often measured during routine blood gas analysis. Endogenous carbon monoxide production has been reported to be increased during sepsis, but carboxyhemoglobin levels have not been thoroughly evaluated as a biomarker of sepsis. We sought to determine whether carboxyhemoglobin levels were elevated during sepsis in a high risk population of premature neonates. We conducted a retrospective cohort study of 30 infants in two neonatal intensive care units using electronic medical and laboratory records. The majority of infants were extremely premature and extremely low birth weight, and 25 had at least one episode of sepsis. We collected all carboxyhemoglobin measurements during their in-patient stay and examined the relationship between carboxyhemoglobin and a variety of clinical and laboratory parameters, in addition to the presence or absence of sepsis, using linear mixed-effect models. We found that postnatal age had the most significant effect on carboxyhemoglobin levels, and other significant associations were identified with gestational age, hemoglobin concentration, oxyhemoglobin saturation, and blood pH. Accounting for these covariates, there was no significant relationship between the onset of sepsis and carboxyhemoglobin levels. Our results show that carboxyhemoglobin is unlikely to be a clinically useful biomarker of sepsis in premature infants, and raise a note of caution about factors which may confound the use of carbon monoxide as a clinical biomarker for other disease processes such as hemolysis.

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

    Science.gov (United States)

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

    2014-06-01

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

  6. Bacteriological profile of neonatal sepsis in a secondary care hospital in rural Tamil Nadu, Southern India

    Directory of Open Access Journals (Sweden)

    Doniparthi Venkata Pavan Kumar

    2017-01-01

    Full Text Available Introduction: Neonatal sepsis is a leading cause of neonatal mortality and morbidity in the world. The objective of the current study was to detect the common causative microorganisms of neonatal sepsis and their antimicrobial resistance patterns in a rural secondary hospital in Tamil Nadu, India. Materials and Methods: Neonates (0–28 days admitted to this newborn care unit from October 2013 to September 2015, with a diagnosis of probable sepsis were studied. All the enrolled babies had blood cultures taken and were followed up till final outcome, which was discharge or death, irrespective of culture result. Univariate analysis was performed for factors associated with culture positivity, generating odds ratios, and confidence intervals. Results: Among the 107 babies with a diagnosis of probable sepsis, 28 (26.2% had shown bacteria in culture. The majority (94.4% were of early-onset sepsis. The predominant organisms were Staphylococcus aureus (10/28 and Klebsiella (6/28. 100% of Gram-negative bacilli and 90% of Staphylococcus were resistant to Ampicillin. Gentamicin resistance among Gram-negative bacilli and Staphylococcus was 52.9% and 20%, respectively, while third-generation cephalosporin resistance was 31.2% and 20%, respectively. Among the neonates diagnosed as probable sepsis, idiopathic prematurity (P = 0.007 was found to have a statistically significant association with culture-positive sepsis. Conclusion: The culture positivity rate among the neonates with probable sepsis in the current study was 26%. An alarmingly high degree of antibiotic resistance observed calls for robust infection control practices and an urgent evaluation and development of individual and national antibiotic policies for neonatal sepsis.

  7. Bacteriological profile of neonatal sepsis in a secondary care hospital in rural Tamil Nadu, Southern India.

    Science.gov (United States)

    Pavan Kumar, Doniparthi Venkata; Mohan, Jesinth; Rakesh, P S; Prasad, Jasmine; Joseph, Lenikumar

    2017-01-01

    Neonatal sepsis is a leading cause of neonatal mortality and morbidity in the world. The objective of the current study was to detect the common causative microorganisms of neonatal sepsis and their antimicrobial resistance patterns in a rural secondary hospital in Tamil Nadu, India. Neonates (0-28 days) admitted to this newborn care unit from October 2013 to September 2015, with a diagnosis of probable sepsis were studied. All the enrolled babies had blood cultures taken and were followed up till final outcome, which was discharge or death, irrespective of culture result. Univariate analysis was performed for factors associated with culture positivity, generating odds ratios, and confidence intervals. Among the 107 babies with a diagnosis of probable sepsis, 28 (26.2%) had shown bacteria in culture. The majority (94.4%) were of early-onset sepsis. The predominant organisms were Staphylococcus aureus (10/28) and Klebsiella (6/28). 100% of Gram-negative bacilli and 90% of Staphylococcus were resistant to Ampicillin. Gentamicin resistance among Gram-negative bacilli and Staphylococcus was 52.9% and 20%, respectively, while third-generation cephalosporin resistance was 31.2% and 20%, respectively. Among the neonates diagnosed as probable sepsis, idiopathic prematurity ( P = 0.007) was found to have a statistically significant association with culture-positive sepsis. The culture positivity rate among the neonates with probable sepsis in the current study was 26%. An alarmingly high degree of antibiotic resistance observed calls for robust infection control practices and an urgent evaluation and development of individual and national antibiotic policies for neonatal sepsis.

  8. Expression and role of neuroglobin in rats with sepsis-associated encephalopathy.

    Science.gov (United States)

    Zhang, Li-Na; Ai, Yu-Hang; Gong, Hua; Guo, Qu-Lian; Huang, Li; Liu, Zhi-Yong; Yao, Bo

    2014-01-01

    To determine the role of neuroglobin in the pathology of sepsis-associated encephalopathy and ascertain if neuroglobin has any protective effects against sepsis-associated encephalopathy. Randomized laboratory animal study. Research university animal laboratory. Two hundred and forty adult male Sprague-Dawley rats. Rats received cecal puncture and ligation (or sham) surgery to induce sepsis, then broken up into groups based on whether or not the rat developed sepsis-associated encephalopathy as determined by electroencephalograph and evoked potential recordings. The rats were then left untreated to examine the effect of sepsis-associated encephalopathy on neuroglobin, treated with a neuroglobin antisense nucleotide to block gene expression, or given hemin, a neuroglobin inducer. Following sepsis induction, diagnosis, and treatment, the brains were analyzed for both gross and ultrastructural morphology. Also, neuronal neuroglobin immunoreactivity and apoptosis (via terminal uridine nucleotide end-labeling) were examined. Blood serum levels were then analyzed for neuroglobin, superoxide dismutase, and malondialdehyde levels. We determined that sepsis-associated encephalopathy induces damage evident when examining both gross and ultrastructural morphology, as well as induces neuronal neuroglobin expression. Also, blockade of neuroglobin expression via antisense treatment will exacerbate these pathological effects, while increasing neuroglobin levels via hemin will ameliorate them. Blood analysis found that levels of superoxide dismutase and malondialdehyde mirrored the level of pathology found in the brain, while plasma neuroglobin levels reflected the amount of neuronal neuroglobin immunoreactivity. We conclude that neuroglobin is involved in the pathogenesis of sepsis-associated encephalopathy and has neuroprotective effects. We also determined that hemin has protective effects against sepsis-associated encephalopathy as well, most probably due to its effect on

  9. Comprehensive Analysis of Gene Expression Profiles of Sepsis-Induced Multiorgan Failure Identified Its Valuable Biomarkers.

    Science.gov (United States)

    Wang, Yumei; Yin, Xiaoling; Yang, Fang

    2018-02-01

    Sepsis is an inflammatory-related disease, and severe sepsis would induce multiorgan dysfunction, which is the most common cause of death of patients in noncoronary intensive care units. Progression of novel therapeutic strategies has proven to be of little impact on the mortality of severe sepsis, and unfortunately, its mechanisms still remain poorly understood. In this study, we analyzed gene expression profiles of severe sepsis with failure of lung, kidney, and liver for the identification of potential biomarkers. We first downloaded the gene expression profiles from the Gene Expression Omnibus and performed preprocessing of raw microarray data sets and identification of differential expression genes (DEGs) through the R programming software; then, significantly enriched functions of DEGs in lung, kidney, and liver failure sepsis samples were obtained from the Database for Annotation, Visualization, and Integrated Discovery; finally, protein-protein interaction network was constructed for DEGs based on the STRING database, and network modules were also obtained through the MCODE cluster method. As a result, lung failure sepsis has the highest number of DEGs of 859, whereas the number of DEGs in kidney and liver failure sepsis samples is 178 and 175, respectively. In addition, 17 overlaps were obtained among the three lists of DEGs. Biological processes related to immune and inflammatory response were found to be significantly enriched in DEGs. Network and module analysis identified four gene clusters in which all or most of genes were upregulated. The expression changes of Icam1 and Socs3 were further validated through quantitative PCR analysis. This study should shed light on the development of sepsis and provide potential therapeutic targets for sepsis-induced multiorgan failure.

  10. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis.

    Science.gov (United States)

    Haydar, Samir; Spanier, Matthew; Weems, Patricia; Wood, Samantha; Strout, Tania

    2017-11-01

    The Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score has been shown to accurately predict mortality in septic patients and is part of recently proposed diagnostic criteria for sepsis. We sought to ascertain the sensitive of the score in diagnosing sepsis, as well as the diagnostic timeliness of the score when compared to traditional systemic inflammatory response syndrome (SIRS) criteria in a population of emergency department (ED) patients treated in the ED, admitted, and subsequently discharged with a diagnosis of sepsis. Electronic health records of 200 patients who were treated for suspected sepsis in our ED and ultimately discharged from our hospital with a diagnosis of sepsis were randomly selected for review from a population of adult ED patients (N=1880). Data extracted included the presence of SIRS criteria and the qSOFA score as well as time required to meet said criteria. In this cohort, 94.5% met SIRS criteria while in the ED whereas only 58.3% met qSOFA. The mean time from arrival to SIRS documentation was 47.1min (95% CI: 36.5-57.8) compared to 84.0min (95% CI: 62.2-105.8) for qSOFA. The median ED "door" to positive SIRS criteria was 12min and 29min for qSOFA. Although qSOFA may be valuable in predicting sepsis-related mortality, it performed poorly as a screening tool for identifying sepsis in the ED. As the time to meet qSOFA criteria was significantly longer than for SIRS, relying on qSOFA alone may delay initiation of evidence-based interventions known to improve sepsis-related outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb® sorbent porous polymer beads.

    Directory of Open Access Journals (Sweden)

    Maryann C Gruda

    Full Text Available Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS, such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS, and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system.Purified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA or control (no bead device in vitro. Except for the TNF-α trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent.This study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions.

  12. Sepsis: emerging role of nitric oxide and selectins Sepse: o papel das selectinas e do óxido nítrico

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    Abhijit Chandra

    2006-02-01

    Full Text Available Sepsis-a state of systemic bacterial infection-often leads to multiorgan failure and is associated with high mortality despite the recent advances achieved in intensive care treatment. Many of the ill effects of sepsis are attributed to an abnormally enhanced host inflammatory response that leads to neutrophil recruitment and activation involving selectins, a class of adhesion molecules, in the initial stages. Nitric oxide and its various isoforms have also been implicated in various vascular alterations and directly participate in the cellular toxicity in sepsis. This review briefly describes the role of selectins and nitric oxide in experimental and clinical sepsis as well as the therapeutic outcomes of blocking therapies.Sepse - um estado de infecção bacteriana sistêmica - frequentemente leva à falência múltipla de órgãos e associa-se a altos índices de mortalidade, apesar de progressos recentes no manejo de pacientes em unidades de terapia intensiva. Muitos dos efeitos maléficos associados à sepse são atribuídos a uma resposta inflamatória patologicamente ampliada que leva a recrutamento neutrofílico e ativação das moléculas de adesão do grupo das selectinas, durante as fases iniciais do processo . O óxido nítrico e sua diversas isoformas também foram implicados nas diversas manifestações vasculares da sepse como participantes diretos da toxicidade celular. Esta revisão descreve o papel das selectinas e do óxido nítrico em situações clínicas e experimentais de sepse, bem como os respectivos efeitos de processos terapêuticos de bloqueio.

  13. Prophylactic Antioxidant Potential of Gallic Acid in Murine Model of Sepsis

    OpenAIRE

    Maurya, Harikesh; Mangal, Vaishali; Gandhi, Sanjay; Prabhu, Kathiresan; Ponnudurai, Kathiresan

    2014-01-01

    Present study is to investigate the effect of Gallic acid pretreatment on survival of septic animals and oxidative stress in different organs like lungs, liver, kidney, spleen, and vascular dysfunction of mice. Sepsis was induced by cecal ligation and puncture (CLP) in healthy adult male albino mice (25–30 g) and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I), SO + sepsis (Group II), and Gallic acid + sepsis (Group III)). Group III animals w...

  14. Community-onset sepsis and its public health burden: a systematic review.

    Science.gov (United States)

    Tsertsvadze, Alexander; Royle, Pam; Seedat, Farah; Cooper, Jennifer; Crosby, Rebecca; McCarthy, Noel

    2016-05-18

    Sepsis is a life-threatening condition and major contributor to public health and economic burden in the industrialised world. The difficulties in accurate diagnosis lead to great variability in estimates of sepsis incidence. There has been even greater uncertainty regarding the incidence of and risk factors for community-onset sepsis (COS). We systematically reviewed the recent evidence on the incidence and risk factors of COS in high income countries (North America, Australasia, and North/Western Europe). Cohort and case-control studies were eligible for inclusion. Medline and Embase databases were searched from 2002 onwards. References of relevant publications were hand-searched. Two reviewers screened titles/abstracts and full-texts independently. One reviewer extracted data and appraised studies which were cross-checked by independent reviewers. Disagreements were resolved via consensus. Odds ratios (ORs) and 95 percent confidence intervals (95 % CIs) were ascertained by type of sepsis (non-severe, severe, and septic shock). Ten cohort and 4 case-control studies were included. There was a wide variation in the incidence (# cases per 100,000 per year) of non-severe sepsis (range: 64-514), severe sepsis (range: 40-455), and septic shock (range: 9-31). Heterogeneity precluded statistical pooling. Two cohort and 4 case-control studies reported risk factors for sepsis. In one case-control and one cohort study, older age and diabetes were associated with increased risk of sepsis. The same case-control study showed an excess risk for sepsis in participants with clinical conditions (e.g., immunosuppression, lung disease, and peripheral artery disease). In one cohort study, higher risk of sepsis was associated with being a nursing home resident (OR = 2.60, 95 % CI: 1.20, 5.60) and in the other cohort study with being physically inactive (OR = 1.33, 95 % CI: 1.13, 1.56) and smoking tobacco (OR = 1.85, 95 % CI: 1.54, 2.22). The evidence on sex, ethnicity, statin use, and

  15. Uterine Sarcoma Presenting with Sepsis from Clostridium perfringens Endometritis in a Postmenopausal Woman

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    Mary J. Kao

    2018-01-01

    Full Text Available Clostridium perfringens is an anaerobic gram positive rod that is found in normal vaginal and cervical flora in 1–10% of healthy women. Uterine infection with Clostridium perfringens is seen rarely but is often related to underlying uterine pathology and can progress quickly to sepsis. Early recognition of sepsis, prompt treatment with antibiotics, and source control with surgical management allow for optimal chance of recovery. We present a case of a postmenopausal woman who presented with sepsis, vaginal bleeding, and back pain who was found to have Clostridium perfringens infection in the setting of undifferentiated uterine sarcoma.

  16. Pneumoretroperitoneum and Sepsis After Transanal Endoscopic Resection of a Rectal Lateral Spreading Tumor

    Science.gov (United States)

    Coura, Marcelo de Melo Andrade; de Almeida, Romulo Medeiros; Moreira, Natascha Mourão; de Sousa, João Batista; de Oliveira, Paulo Gonçalves

    2017-01-01

    Transanal endoscopic microsurgery is considered a safe, appropriate, and minimally invasive approach, and complications after endoscopic microsurgery are rare. We report a case of sepsis and pneumoretroperitoneum after resection of a rectal lateral spreading tumor. The patient presented with rectal mucous discharge. Colonoscopy revealed a rectal lateral spreading tumor. The patient underwent an endoscopic transanal resection of the lesion. He presented with sepsis of the abdominal focus, and imaging tests revealed pneumoretroperitoneum. A new surgical intervention was performed with a loop colostomy. Despite the existence of other reports on pneumoretroperitoneum after transanal endoscopic microsurgery, what draws attention to this case is the association with sepsis. PMID:28761873

  17. Forøget renal udskillelse af antibiotika kan resultere i underdosering ved sepsis

    DEFF Research Database (Denmark)

    Moser, Claus; Hartvig, Tom; Schierbeck, Jens

    2016-01-01

    Early, relevant antibiotic treatment is of pivotal significance for survival for patients with sepsis. Recent reports reveal, that critically ill patients may need substantially higher dosing of antibiotics than the usual standards. The background is the newly described augmented renal clearance...... (ARC), which can be observed in critically ill patients with sepsis. ARC results in significantly reduced antibiotic concentrations in patients with sepsis and can potentially have fatal consequences. The purpose of this paper is to make medical doctors aware of the phenomenon and to compensate...

  18. Correlation between measured energy expenditure and clinically obtained variables in trauma and sepsis patients.

    Science.gov (United States)

    Frankenfield, D C; Omert, L A; Badellino, M M; Wiles, C E; Bagley, S M; Goodarzi, S; Siegel, J H

    1994-01-01

    Indirect calorimetry is the preferred method for determining caloric requirements of patients, but availability of the device is limited by high cost. A study was therefore conducted to determine whether clinically obtainable variables could be used to predict metabolic rate. Patients with severe trauma or sepsis who required mechanical ventilation were measured by an open-circuit indirect calorimeter. Several clinical variables were obtained simultaneously. Measurements were repeated every 12 hours for up to 10 days. Twenty-six trauma and 30 sepsis patients were measured 423 times. Mean resting energy expenditure was 36 +/- 7 kcal/kg (trauma) vs 45 +/- 8 kcal/kg (sepsis) (p types.

  19. Clavanin bacterial sepsis control using a novel methacrylate nanocarrier

    Directory of Open Access Journals (Sweden)

    Saúde ACM

    2014-10-01

    Full Text Available Amanda CM Saúde,1 Alicia S Ombredane,1 Osmar N Silva,1 João ARG Barbosa,1,2 Susana E Moreno,3 Ana Claudia Guerra Araujo,4 Rosana Falcão,4 Luciano P Silva,4 Simoni C Dias,1 Octávio L Franco1,3 1Programa de Pós Graduação em Ciências Genômicas e Biotecnologia, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília, FD, Brazil; 2Laboratório de Biofísica-Departamento de Biologia Celular-IB, Universidade de Brasília – UNB, DF, Brazil; 3Universidade Católica Dom Bosco – UCDB, Campo Grande, MS, Brazil; 4Empresa Brasileira de Pesquisa Agropecuária – EMBRAPA – Recursos Genéticos e Biotecnologia, Brasília, DF, Brazil Abstract: Controlling human pathogenic bacteria is a worldwide problem due to increasing bacterial resistance. This has prompted a number of studies investigating peptides isolated from marine animals as a possible alternative for control of human pathogen infections. Clavanins are antimicrobial peptides isolated from the marine tunicate Styela clava, showing 23 amino acid residues in length, cationic properties, and also high bactericidal activity. In spite of clear benefits from the use of peptides, currently 95% of peptide properties have limited pharmaceutical applicability, such as low solubility and short half-life in the circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in order to develop nanoantibiotics against bacterial sepsis. Clavanin was nanostructured using EUDRAGIT® L 100-55 and RS 30 D solution (3:1 w:w. Atomic force, scanning electron microscopy and dynamic light scattering showed nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of -7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was assessed by reversed-phase chromatography. In vitro bioassays showed that the nanostructured clavanin was partially able to control development of Staphylococcus aureus, Klebsiella pneumoniae, and

  20. Treatment of sepsis: current status of clinical immunotherapy.

    LENUS (Irish Health Repository)

    O'Callaghan, A

    2012-02-03

    While antibiotics address the root cause of sepsis--that of pathogen infection--they fail to provide an adequate cure for the condition. Currently, 30% to 50% of septic patients die, and this figure is likely to increase in line with the proliferation of multi-drug resistant bacteria. With an increased understanding of the immune response, it has been proposed that modulation of this defence mechanism offers the best hope of cure. Many entry-points in the immune system have been identified and targeted therapies have been developed,but why are these not in routine clinical practice? This review examines the latest evidence for the use of immuno-modulating drugs, obtained from human clinical trials. We discuss cytokine-based therapies, steroids and anti-coagulants. Finally, consideration is given as to why successful therapies in the laboratory, and in vivo models, do not automatically translate into clinical benefit

  1. Apoptosis-induced lymphopenia in sepsis and other severe injuries.

    Science.gov (United States)

    Girardot, Thibaut; Rimmelé, Thomas; Venet, Fabienne; Monneret, Guillaume

    2017-02-01

    Sepsis and other acute injuries such as severe trauma, extensive burns, or major surgeries, are usually followed by a period of marked immunosuppression. In particular, while lymphocytes play a pivotal role in immune response, their functions and numbers are profoundly altered after severe injuries. Apoptosis plays a central role in this process by affecting immune response at various levels. Indeed, apoptosis-induced lymphopenia duration and depth have been associated with higher risk of infection and mortality in various clinical settings. Therapies modulating apoptosis represent an interesting approach to restore immune competence after acute injury, although their use in clinical practice still presents several limitations. After briefly describing the apoptosis process in physiology and during severe injuries, we will explore the immunological consequences of injury-induced lymphocyte apoptosis, and describe associations with clinically relevant outcomes in patients. Therapeutic perspectives targeting apoptosis will also be discussed.

  2. Marine Compounds with Therapeutic Potential in Gram-Negative Sepsis

    Directory of Open Access Journals (Sweden)

    Irina Yermak

    2013-06-01

    Full Text Available This paper concerns the potential use of compounds, including lipid A, chitosan, and carrageenan, from marine sources as agents for treating endotoxemic complications from Gram-negative infections, such as sepsis and endotoxic shock. Lipid A, which can be isolated from various species of marine bacteria, is a potential antagonist of bacterial endotoxins (lipopolysaccharide (LPSs. Chitosan is a widespread marine polysaccharide that is derived from chitin, the major component of crustacean shells. The potential of chitosan as an LPS-binding and endotoxin-neutralizing agent is also examined in this paper, including a discussion on the generation of hydrophobic chitosan derivatives to increase the binding affinity of chitosan to LPS. In addition, the ability of carrageenan, which is the polysaccharide of red alga, to decrease the toxicity of LPS is discussed. We also review data obtained using animal models that demonstrate the potency of carrageenan and chitosan as antiendotoxin agents.

  3. Sepsis and siderosis, Yersinia enterocolitica and hereditary haemochromatosis.

    Science.gov (United States)

    Thwaites, Phoebe A; Woods, Marion L

    2017-01-04

    A 60-year-old woman was admitted with sepsis, relative bradycardia, CT evidence of numerous small liver abscesses and 'skin bronzing' consistent with hereditary haemochromatosis (HH). Yersinia enterocolitica O:9 infection was confirmed by serology specimens taken 10 days apart. Iron overload was detected, and homozygous C282Y gene mutation confirmed HH. Liver biopsy revealed grade IV siderosis with micronodular cirrhosis. Haemochromatosis is a common, inherited disorder leading to iron overload that can produce end-organ damage from excess iron deposition. Haemochromatosis diagnosis allowed aggressive medical management with phlebotomy achieving normalisation of iron stores. Screening for complications of cirrhosis was started that included hepatoma surveillance. Iron overload states are known to increase patient susceptibility to infections caused by lower virulence bacteria lacking sophisticated iron metabolism pathways, for example, Yersinia enterocolitica Although these serious disseminated infections are rare, they may serve as markers for occult iron overload and should prompt haemochromatosis screening. 2017 BMJ Publishing Group Ltd.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

  5. Non-traumatic abdominal emergencies: imaging and intervention in sepsis

    International Nuclear Information System (INIS)

    Lee, M.J.

    2002-01-01

    Cross-sectional imaging, in particular CT, has become the main method of detecting abdominal collections. Indium-labelled white-cell scintigraphy and gallium scintigraphy are reserved for patients in whom there is a high clinical suspicion of abdominal sepsis but CT has not revealed a source of sepsis. Scintigraphy is also used in patients with suspected vascular graft infections or suspected infected hip prostheses. Percutaneous abscess drainage (PAD) has revolutionised the treatment of abdominal abscesses over the past 20 years, with repeat laparotomy for postoperative abscesses becoming a rare event. Ultrasound or CT can be used to guide PAD. Choosing an access route that does not cross intervening organs is of crucial importance to the safe performance of PAD. The Trocar or Seldinger techniques can be used with equal success. The cavity should be aspirated until dry and irrigated with saline. Repeat imaging after drainage is helpful to detect any undrained locules. PAD endpoints include patient defervescence, reduction in white blood cell count and catheter drainage of less than 10 ml per day. Details regarding PAD in specific abdominal regions are discussed. Success rates for PAD are high (close to 90%) in most abdominal organs. Slightly lower success rates are seen with PAD of pancreatic abscesses and abscesses associated with fistulas (60-85% success rates). Complication rates lie between 0% and 10%. Complications can be minimised by ensuring that the patient has broad spectrum antibiotic coverage before drainage, by carefully planning the access route and by ensuring diligent post-procedure care by radiology staff. (orig.)

  6. Australasian Resuscitation In Sepsis Evaluation trial statistical analysis plan.

    Science.gov (United States)

    Delaney, Anthony; Peake, Sandra L; Bellomo, Rinaldo; Cameron, Peter; Holdgate, Anna; Howe, Belinda; Higgins, Alisa; Presneill, Jeffrey; Webb, Steve

    2013-10-01

    The Australasian Resuscitation In Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the ED with severe sepsis. In keeping with current practice, and taking into considerations aspects of trial design and reporting specific to non-pharmacologic interventions, this document outlines the principles and methods for analysing and reporting the trial results. The document is prepared prior to completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and prior to completion of the two related international studies. The statistical analysis plan was designed by the ARISE chief investigators, and reviewed and approved by the ARISE steering committee. The data collected by the research team as specified in the study protocol, and detailed in the study case report form were reviewed. Information related to baseline characteristics, characteristics of delivery of the trial interventions, details of resuscitation and other related therapies, and other relevant data are described with appropriate comparisons between groups. The primary, secondary and tertiary outcomes for the study are defined, with description of the planned statistical analyses. A statistical analysis plan was developed, along with a trial profile, mock-up tables and figures. A plan for presenting baseline characteristics, microbiological and antibiotic therapy, details of the interventions, processes of care and concomitant therapies, along with adverse events are described. The primary, secondary and tertiary outcomes are described along with identification of subgroups to be analysed. A statistical analysis plan for the ARISE study has been developed, and is available in the public domain, prior to the completion of recruitment into the

  7. Reposição de volume na sepse com solução salina hipertônica Sepsis volume reposition with hypertonic saline solution

    Directory of Open Access Journals (Sweden)

    Gilberto Friedman

    2008-09-01

    Full Text Available Esta revisão discute os efeitos hemodinâmicos e imunomoduladores da solução hipertônica em choque experimental e em pacientes com sepse. Comentamos sobre os mecanismos de ação da solução hipertônica, recorrendo a dados sobre choque hemorrágico e séptico. Atuações específicas da solução salina hipertônica aplicáveis a sepse grave e choque séptico são enfatizadas. Os dados disponíveis corroboram os benefícios em potencial da infusão de solução salina hipertônica em vários aspetos da fisiopatologia da sepse, inclusive hipoperfusão dos tecidos, consumo reduzido de oxigênio, disfunção endotelial, depressão miocárdica e presença de um amplo elenco de citocinas próinflamatórias e várias espécies de oxidantes. Uma terapia que, ao mesmo tempo, bloqueie os componentes prejudiciais da sepse terá um impacto no seu tratamento. Estudos prospectivos adequadamente desenhados poderão no futuro comprovar o papel benéfico da solução salina hipertônica.The present review discusses the hemodynamic and immune-modulatory effects of hypertonic saline in experimental shock and in patients with sepsis. We comment on the mechanisms of action of hypertonic saline, calling upon data in hemorrhagic and septic shock. Specific actions of hypertonic saline applicable to severe sepsis and septic shock are highlighted. Data available support potential benefits of hypertonic saline infusion in various aspects of the pathophysiology of sepsis, including tissue hypoperfusion, decreased oxygen consumption, endothelial dysfunction, cardiac depression, and the presence of a broad array of pro-inflammatory cytokines and various oxidant species. A therapy that simultaneously blocks the damaging components of sepsis will have an impact on the management of sepsis. Proper designed prospective studies may prove a beneficial role for hypertonic saline solution in the future.

  8. It Is Not Just Folklore: The Aqueous Extract of Mung Bean Coat Is Protective against Sepsis

    Directory of Open Access Journals (Sweden)

    Shu Zhu

    2012-01-01

    Full Text Available Mung bean (Vigna Radiata has been traditionally used in China both as nutritional food and herbal medicine against a number of inflammatory conditions since the 1050s. A nucleosomal protein, HMGB1, has recently been established as a late mediator of lethal systemic inflammation with a relatively wider therapeutic window for pharmacological interventions. Here we explored the HMGB1-inhibiting capacity and therapeutic potential of mung bean coat (MBC extract in vitro and in vivo. We found that MBC extract dose-dependently attenuated LPS-induced release of HMGB1 and several chemokines in macrophage cultures. Oral administration of MBC extract significantly increased animal survival rates from 29.4% (in saline group, N=17 mice to 70% (in experimental MBC extract group, N=17 mice, P<0.05. In vitro, MBC extract stimulated HMGB1 protein aggregation and facilitated both the formation of microtubule-associatedprotein-1-light-chain-3-(LC3-containing cytoplasmic vesicles, and the production of LC3-II in macrophage cultures. Consequently, MBC extract treatment led to reduction of cellular HMGB1 levels in macrophage cultures, which was impaired by coaddition of two autophagy inhibitors (bafilomycin A1 and 3-methyladenine. Conclusion. MBC extract is protective against lethal sepsis possibly by stimulating autophagic HMGB1 degradation.

  9. Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury.

    Directory of Open Access Journals (Sweden)

    Marialbert Acosta-Herrera

    Full Text Available Acute lung injury (ALI is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV using low tidal volumes (LVT plus moderate to high levels of positive end-expiratory pressure (PEEP. However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The 'response to microorganisms' was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the 'neuron projection morphogenesis' process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir-27a, Mir-103, Mir-17-5p and Mir-130a were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated. Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection

  10. Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury

    Science.gov (United States)

    Acosta-Herrera, Marialbert; Lorenzo-Diaz, Fabian; Pino-Yanes, Maria; Corrales, Almudena; Valladares, Francisco; Klassert, Tilman E.; Valladares, Basilio; Slevogt, Hortense; Ma, Shwu-Fan

    2015-01-01

    Acute lung injury (ALI) is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV) using low tidal volumes (LVT) plus moderate to high levels of positive end-expiratory pressure (PEEP). However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg) plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg) plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The ‘response to microorganisms’ was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the ‘neuron projection morphogenesis’ process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated). Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection

  11. Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury

    Science.gov (United States)

    Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R.; Merriman, Joseph A.; Stach, Christopher S.; Horswill, Alexander R.; Peterson, Marnie L.; Schlievert, Patrick M.

    2013-01-01

    ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. PMID:23963178

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

    Directory of Open Access Journals (Sweden)

    Pablo Sibaja

    2017-01-01

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

  13. Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.

    NARCIS (Netherlands)

    Flier, M. van der; Baerveldt, E.M.; Miedema, A.; Hartwig, N.G.; Hazelzet, J.A.; Emonts, M.; Groot, R. de; Prens, E.P.; Vught, A.J. van; Jansen, N.J.

    2013-01-01

    OBJECTIVES: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis. DESIGN: Observational study. SETTING: Two tertiary academic children hospital PICUs.

  14. Relationship between sublingual and intestinal microcirculatory perfusion in patients with abdominal sepsis

    NARCIS (Netherlands)

    Boerma, E. Christiaan; van der Voort, Peter H. J.; Spronk, Peter E.; Ince, Can

    2007-01-01

    Objective: To evaluate the relation between sublingual and intestinal microcirculatory alterations in patients with abdominal sepsis. Design. Prospective observational study. Setting. A 23-bed mixed intensive care unit of a tertiary teaching hospital. Patients: Twenty-three patients with abdominal

  15. New strategy for sepsis: Targeting a key role of platelet-neutrophil interaction

    Directory of Open Access Journals (Sweden)

    Xu Wang

    2014-07-01

    Full Text Available Neutrophil and platelet are essential arms of the innate immune response. In sepsis, platelet abnormal activation as well as neutrophil paralysis are well recognized. For platelet, it is characterized by the contribution to disseminated intravascular coagulation (DIC and the enhanced inflammation response. In terms of neutrophil, its dysfunction is manifested by the impaired recruitment and migration to the infectious foci, abnormal sequestration in the remote organs, and the delayed clearance. More recently, it has been apparent that together platelet-neutrophil interaction can induce a faster and harder response during sepsis. This article focuses on the activation of platelet, dysfunction of neutrophil, and the interaction between them during sepsis and profiles some of the molecular mechanisms and outcomes in these cellular dialogues, providing a novel strategy for treatment of sepsis.

  16. The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

    Directory of Open Access Journals (Sweden)

    Georgescu Anca Meda

    2017-02-01

    Full Text Available Sepsis is an injurious systemic host response to infection, which can often lead to septic shock and death. Recently, the immune-pathogenesis and genomics of sepsis have become a research topic focusing on the establishment of diagnostic and prognostic biomarkers. As yet, none have been identified as having the necessary specificity to be used independently of other factors in this respect. However the accumulation of current evidence regarding genetic variations, especially the single nucleotide polymorphisms (SNPs of cytokines and other innate immunity determinants, partially explains the susceptibility and individual differences of patients with regard to the evolution of sepsis. This article outlines the role of genetic variation of some serum proteins which have the potential to be used as biomarker values in evaluating sepsis susceptibility and the progression of the condition.

  17. [CONTEMPORARY MOLECULAR-GENETIC METHODS USED FOR ETIOLOGIC DIAGNOSTICS OF SEPSIS].

    Science.gov (United States)

    Gavrilov, S N; Skachkova, T S; Shipulina, O Yu; Savochkina, Yu A; Shipulin, G A; Maleev, V V

    2016-01-01

    Etiologic diagnostics of sepsis is one of the most difficult problems of contemporary medicine due to a wide variety of sepsis causative agents, many of which are components of normal human microflora. Disadvantages of contemporary "golden standard" of microbiologic diagnostics of sepsis etiology by seeding of blood for sterility are duration of cultivation, limitation in detection of non-cultivable forms of microorganisms, significant effect of preliminary empiric antibiotics therapy on results of the analysis. Methods of molecular diagnostics that are being actively developed and integrated during the last decade are deprived of these disadvantages. Main contemporary methods of molecular-biological diagnostics are examined in the review, actualdata on their diagnostic characteristic are provided. Special attention is given to methods of PCR-diagnostics, including novel Russian developments. Methods of nucleic acid hybridization and proteomic analysis are examined in comparative aspect. Evaluation of application and perspectives of development of methods of molecular diagnostics of sepsis is given.

  18. High Levels of Methylarginines Were Associated With Increased Mortality in Patients With Severe Sepsis

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  19. A study on the outcome of neonates with sepsis at the Lagos ...

    African Journals Online (AJOL)

    MJP

    2015-04-18

    Apr 18, 2015 ... occurs in developing countries with neonatal ... mortality rate in our environment due to sepsis to be 15.7%. Risk factors for a poor outcome include low birth weight, perinatal period, and maternal illness in pregnancy.

  20. MR imaging findings of lower extremity sepsis caused by vibro vulnificus: A report of three cases

    International Nuclear Information System (INIS)

    Kim, Jihyun; Koh, Sung Hye; Min, Soo Kee; Lee, Jeong A; Lee, Kwan Seop

    2017-01-01

    Lower extremity infection caused by Vibrio vulnificus sepsis is a rapidly progressing fatal condition. Prompt diagnosis followed by early and aggressive treatment with antibiotics and fasciotomy is crucial. In this report, we described lower extremity magnetic resonance (MR) images of three patients with Vibrio vulnificus sepsis. In our cases, MR imaging of lower extremity with Vibrio vulnificus sepsis showed three common findings. First, the MR signal abnormalities appeared simultaneously in all layers, including skin, subcutaneous fat, muscles, and deep fasciae. Second, the inflammation showed symmetry on both legs. Third, none of our cases was accompanied by abscess formation. These imaging features may represent rapid progression of Vibrio vulnificus sepsis and could be helpful for accurate diagnosis, and prompt and aggressive treatment

  1. Serum calprotectin as a diagnostic marker of late onset sepsis in full ...

    African Journals Online (AJOL)

    EL-HAKIM

    r=0.95) and ... Pediatrics, and. Clinical Pathology*, ... clinically suspected sepsis, pneumonia as diagnosed by X ray or by microscopic or cultural evidence in tracheal aspirate ... Systems, Minneapolis, MN, USA), the detection limit of the assay, ...

  2. Lactoferrin and neonatology - role in neonatal sepsis and necrotizing enterocolitis: present, past and future.

    Science.gov (United States)

    Sharma, Deepak; Shastri, Sweta

    2016-03-01

    Neonatal sepsis and necrotizing enterocolitis (NEC) are two most important neonatal problems in nursery which constitute the bulk of neonatal mortality and morbidity. Inflammatory mediators secondary to sepsis and NEC increases morbidity, by affecting various system of body like lung, brain and eye, thus causing long term implications. Lactoferrin (LF) is a component of breast milk and multiple actions that includes antimicrobial, antiviral, anti-fungal and anti-cancer and various other actions. Few studies have been completed and a number of them are in progress for evaluation of efficacy and safety of LF in the prevention of neonatal sepsis and NEC in field of neonatology. In future, LF prophylaxis and therapy may have a significant impact in improving clinical outcomes of vulnerable preterm neonates. This review analyse the role of lactoferrin in prevention of neonatal sepsis and NEC, with emphasis on mechanism of action, recent studies and current studies going on around the globe.

  3. Histone deacetylase inhibitor treatment attenuates coagulation imbalance in a lethal murine model of sepsis

    DEFF Research Database (Denmark)

    Zhao, Ting; Li, Yongqing; Liu, Baoling

    2014-01-01

    BACKGROUND: Sepsis has a profound impact on the inflammatory and hemostatic systems. In addition to systemic inflammation, it can produce disseminated intravascular coagulation, microvascular thrombosis, consumptive coagulopathy, and multiple organ failure. We have shown that treatment with suber...

  4. A study on the outcome of neonates with sepsis at the Lagos ...

    African Journals Online (AJOL)

    MJP

    2015-04-18

    Apr 18, 2015 ... patients' outcome with respect to sepsis in neonates. Methods: This was a prospective ..... Conflict of Interest: None declared. Submit your valuable ... Rigorous, constructive and unbiased peer-review. • No space constraints or ...

  5. Recent advances in prevention of sepsis in the premature neonates in NICU.

    Science.gov (United States)

    Manzoni, P; Rizzollo, S; Decembrino, L; Ruffinazzi, G; Rossi Ricci, A; Gallo, E; Stolfi, I; Mostert, M; Stronati, M; Farina, D

    2011-03-01

    Sepsis-related morbidity and mortality are major problems in NICU. Preterm neonates display clinical characteristics that make them prone to infections. Due to the high frequency of severe neurodevelopmental sequelae in survivors, the best possible strategy to manage sepsis in NICU is to prevent them. Hygiene, cohorting, stewardship on use of H2-blockers, steroids and broad-spectrum antibiotic are mandatory, as well as proper management of central venous accesses and surgical devices. In addition, clinical research offers the opportunity of adopting pharmacological preventative strategies such as use of palivizumab to prevent RSV infection, use of fluconazole to prevent fungal sepsis, use of probiotics and lactoferrin to enhance the innate immunity, and use of pagibaximab to prevent staphylococcal sepsis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. MR imaging findings of lower extremity sepsis caused by vibro vulnificus: A report of three cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihyun; Koh, Sung Hye; Min, Soo Kee; Lee, Jeong A; Lee, Kwan Seop [Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2017-01-15

    Lower extremity infection caused by Vibrio vulnificus sepsis is a rapidly progressing fatal condition. Prompt diagnosis followed by early and aggressive treatment with antibiotics and fasciotomy is crucial. In this report, we described lower extremity magnetic resonance (MR) images of three patients with Vibrio vulnificus sepsis. In our cases, MR imaging of lower extremity with Vibrio vulnificus sepsis showed three common findings. First, the MR signal abnormalities appeared simultaneously in all layers, including skin, subcutaneous fat, muscles, and deep fasciae. Second, the inflammation showed symmetry on both legs. Third, none of our cases was accompanied by abscess formation. These imaging features may represent rapid progression of Vibrio vulnificus sepsis and could be helpful for accurate diagnosis, and prompt and aggressive treatment.

  7. Antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction.

    Science.gov (United States)

    Ishimaru, Naoto; Ohnishi, Hisashi; Nishiuma, Teruaki; Doukuni, Ryota; Umezawa, Kanoko; Oozone, Sachiko; Kuramoto, Emi; Yoshimura, Sho; Kinami, Saori

    2013-01-01

    Streptococcus pneumoniae is a rare pathogen of sepsis in patients with antithyroid drug-induced agranulocytosis. We herein describe a case of antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction. A 27-year-old woman who was previously prescribed methimazole for nine months presented with a four-day history of a sore throat. She nearly choked and was diagnosed with febrile agranulocytosis. She was successfully treated with intubation, intravenous antibiotics and granulocyte colony-stimulating factor. Her blood cultures yielded S. pneumoniae. Emergency airway management, treatment of sepsis and the administration of granulocyte colony-stimulating factor can improve the clinical course of antithyroid drug-induced pneumococcal sepsis in patients with airway obstruction.

  8. Insulin accelerates global and mitochondrial protein synthesis rates in neonatal muscle during sepsis

    Science.gov (United States)

    In neonatal pigs, sepsis decreases protein synthesis in skeletal muscle by decreasing translation initiation. However, insulin stimulates muscle protein synthesis despite persistent repression of translation initiation signaling. To determine whether the insulin-induced increase in global rates of m...

  9. Changes of serum procalcitonin (PCT) and IL-6 levels in patients with sepsis

    International Nuclear Information System (INIS)

    Wang Jinjiang

    2007-01-01

    Objective: To investigate the importance of determination of changes of serum procalcitonin (PCT) and IL-6 levels in patients with sepsis. Methods: Serum PCT (with double-sandwich immunofluorescence assay) and IL-6 (with ELISA) levels were measured repeatedly in 130 patients with sepsis on d1, d3, d5, d7 after admission. Values in 130 healthy individuals were also measured as control. Results: The serum levels of PCT and IL-6 in the patients with sepsis of admission were significantly higher than those in controls. The levels dropped markedly in the survivors by d7. Among the septic patients, the levels in the succumbed patients were significantly higher those in the survivors (P<0.05). Conclusion: Serum PCT and IL-6 values appeared to be of prognostic value in patients with sepsis. (authors)

  10. Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: a meta-analysis.

    Science.gov (United States)

    Fang, Fang; Pan, Jian; Li, Yiping; Xu, Lixiao; Su, Guanghao; Li, Gang; Wang, Jian

    2015-01-01

    Many studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Relevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Significant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR=0.75, 95% CI=0.59-0.94) and severe sepsis subgroup for LL+L2 versus 22 (OR=0.67, 95% CI=0.47-0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models. According to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality. Copyright © 2014. Published by Elsevier Inc.

  11. Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin

    Directory of Open Access Journals (Sweden)

    Moro Serrano Manuel

    2006-05-01

    Full Text Available Abstract Background It has recently been suggested that serum procalcitonin (PCT is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. Methods One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC curves. The Youden's index (sensitivity + specificity - 1 was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI were calculated. Results The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%; 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%, and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%. Conclusion Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of

  12. Continuous multi-parameter heart rate variability analysis heralds onset of sepsis in adults.

    Directory of Open Access Journals (Sweden)

    Saif Ahmad

    Full Text Available BACKGROUND: Early diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis. METHODOLOGY/PRINCIPAL FINDINGS: We monitored heart rate continuously in adult bone marrow transplant (BMT patients (n = 21 beginning a day before their BMT and continuing until recovery or withdrawal (12+/-4 days. We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment. Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25% reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (n = 14, wavelet HRV demonstrated a 25% drop from

  13. Fine Particulate Matter Pollution and Risk of Community-Acquired Sepsis.

    Science.gov (United States)

    Sarmiento, Elisa J; Moore, Justin Xavier; McClure, Leslie A; Griffin, Russell; Al-Hamdan, Mohammad Z; Wang, Henry E

    2018-04-21

    While air pollution has been associated with health complications, its effect on sepsis risk is unknown. We examined the association between fine particulate matter (PM 2.5 ) air pollution and risk of sepsis hospitalization. We analyzed data from the 30,239 community-dwelling adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort linked with satellite-derived measures of PM 2.5 data. We defined sepsis as a hospital admission for a serious infection with ≥2 systemic inflammatory response (SIRS) criteria. We performed incidence density sampling to match sepsis cases with 4 controls by age (±5 years), sex, and race. For each matched group we calculated mean daily PM 2.5 exposures for short-term (30-day) and long-term (one-year) periods preceding the sepsis event. We used conditional logistic regression to evaluate the association between PM 2.5 exposure and sepsis, adjusting for education, income, region, temperature, urbanicity, tobacco and alcohol use, and medical conditions. We matched 1386 sepsis cases with 5544 non-sepsis controls. Mean 30-day PM 2.5 exposure levels (Cases 12.44 vs. Controls 12.34 µg/m³; p = 0.28) and mean one-year PM 2.5 exposure levels (Cases 12.53 vs. Controls 12.50 µg/m³; p = 0.66) were similar between cases and controls. In adjusted models, there were no associations between 30-day PM 2.5 exposure levels and sepsis (4th vs. 1st quartiles OR: 1.06, 95% CI: 0.85⁻1.32). Similarly, there were no associations between one-year PM 2.5 exposure levels and sepsis risk (4th vs. 1st quartiles OR: 0.96, 95% CI: 0.78⁻1.18). In the REGARDS cohort, PM 2.5 air pollution exposure was not associated with risk of sepsis.

  14. Validation and optimisation of an ICD-10-coded case definition for sepsis using administrative health data

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    Jolley, Rachel J; Jetté, Nathalie; Sawka, Keri Jo; Diep, Lucy; Goliath, Jade; Roberts, Derek J; Yipp, Bryan G; Doig, Christopher J

    2015-01-01

    Objective Administrative health data are important for health services and outcomes research. We optimised and validated in intensive care unit (ICU) patients an International Classification of Disease (ICD)-coded case definition for sepsis, and compared this with an existing definition. We also assessed the definition's performance in non-ICU (ward) patients. Setting and participants All adults (aged ≥18 years) admitted to a multisystem ICU with general medicosurgical ICU care from one of three tertiary care centres in the Calgary region in Alberta, Canada, between 1 January 2009 and 31 December 2012 were included. Research design Patient medical records were randomly selected and linked to the discharge abstract database. In ICU patients, we validated the Canadian Institute for Health Information (CIHI) ICD-10-CA (Canadian Revision)-coded definition for sepsis and severe sepsis against a reference standard medical chart review, and optimised this algorithm through examination of other conditions apparent in sepsis. Measures Sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results Sepsis was present in 604 of 1001 ICU patients (60.4%). The CIHI ICD-10-CA-coded definition for sepsis had Sn (46.4%), Sp (98.7%), PPV (98.2%) and NPV (54.7%); and for severe sepsis had Sn (47.2%), Sp (97.5%), PPV (95.3%) and NPV (63.2%). The optimised ICD-coded algorithm for sepsis increased Sn by 25.5% and NPV by 11.9% with slightly lowered Sp (85.4%) and PPV (88.2%). For severe sepsis both Sn (65.1%) and NPV (70.1%) increased, while Sp (88.2%) and PPV (85.6%) decreased slightly. Conclusions This study demonstrates that sepsis is highly undercoded in administrative data, thus under-ascertaining the true incidence of sepsis. The optimised ICD-coded definition has a higher validity with higher Sn and should be preferentially considered if used for surveillance purposes. PMID:26700284

  15. Comparative study of the prevalence of sepsis in patients admitted to dermatology and internal medicine wards*

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    Almeida, Luiz Maurício Costa; Diniz, Michelle dos Santos; Diniz, Lorena dos Santos; Machado-Pinto, Jackson; Silva, Francisco Chagas Lima

    2013-01-01

    BACKGROUND Sepsis is a common cause of morbidity and mortality among hospitalized patients. The prevalence of this condition has increased significantly in different parts of the world. Patients admitted to dermatology wards often have severe loss of skin barrier and use systemic corticosteroids, which favor the development of sepsis. OBJECTIVES To evaluate the prevalence of sepsis among patients admitted to a dermatology ward compared to that among patients admitted to an internal medicine ward. METHODS It is a cross-sectional, observational, comparative study that was conducted at Hospital Santa Casa de Belo Horizonte. Data were collected from all patients admitted to four hospital beds at the dermatology and internal medicine wards between July 2008 and July 2009. Medical records were analyzed for the occurrence of sepsis, dermatologic diagnoses, comorbidities, types of pathogens and most commonly used antibiotics. RESULTS We analyzed 185 medical records. The prevalence of sepsis was 7.6% among patients admitted to the dermatology ward and 2.2% (p = 0.10) among those admitted to the internal medicine ward. Patients with comorbidities, diabetes mellitus and cancer did not show a higher incidence of sepsis. The main agent found was Staphylococcus aureus, and the most commonly used antibiotics were ciprofloxacin and oxacillin. There was a significant association between sepsis and the use of systemic corticosteroids (p <0.001). CONCLUSION It becomes clear that epidemiological studies on sepsis should be performed more extensively and accurately in Brazil so that efforts to prevent and treat this serious disease can be made more effectively. PMID:24173179

  16. A pathological study of sepsis associated with sarcoptic mange in raccoon dogs (Nyctereutes procyonoides) in Japan.

    Science.gov (United States)

    Nakagawa, T L D R; Takai, Y; Kubo, M; Sakai, H; Masegi, T; Yanai, T

    2009-01-01

    The pathological findings in Japanese raccoon dogs with sarcoptic mange infection associated with death from sepsis are described. Microscopical lesions of the skin were consistent with those described previously in wildlife populations with Sarcoptes infection, but secondary lesions were also present in the lungs, heart, kidneys, liver, spleen and brain of these animals. This infection was therefore very similar to "crusted scabies" or "Norwegian scabies" in man and was characterized by severe pathology and high mortality, with deaths frequently occurring due to sepsis.

  17. Implementation of an Emergency Department Sepsis Bundle and System Redesign: A Process Improvement Initiative.

    Science.gov (United States)

    McColl, Tamara; Gatien, Mathieu; Calder, Lisa; Yadav, Krishan; Tam, Ryan; Ong, Melody; Taljaard, Monica; Stiell, Ian

    2017-03-01

    In 2008-2009, the Canadian Institute for Health Information reported over 30,000 cases of sepsis hospitalizations in Canada, an increase of almost 4,000 from 2005. Mortality rates from severe sepsis and septic shock continue to remain greater than 30% in Canada and are significantly higher than other critical conditions treated in the emergency department (ED). Our group formed a multidisciplinary sepsis committee, conducted an ED process of care analysis, and developed a quality improvement protocol. The objective of this study was to evaluate the effects of this sepsis management bundle on patient mortality. This before and after study was conducted in two large Canadian tertiary care EDs and included adult patients with suspected severe infection that met at least two systemic inflammatory response syndrome (SIRS) criteria. We studied the implementation of a sepsis bundle including triage flagging, RN medical directive, education campaign, and a modified sepsis protocol. The primary outcomes were 30-day all-cause mortality and sepsis protocol use. We included a total of 167 and 185 patients in the pre- and post-intervention analysis, respectively. Compared to the pre-intervention group, mortality was significantly lower in the post-intervention group (30.7% versus 17.3%; absolute difference, 13.4%; 95% CI 9.8-17.0; p=0.006). There was also a higher rate of sepsis protocol use in the post-intervention group (20.3% versus 80.5%, absolute difference 60.2%; 95% CI 55.1-65.3; pimproved early identification and protocolized medical care, was associated with improved time to achieve key therapeutic interventions and a reduction in 30-day mortality. Similar low-cost initiatives could be implemented in other EDs to potentially improve outcomes for this high-risk group of patients.

  18. Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

    International Nuclear Information System (INIS)

    Hasselgren, P.O.; Chen, I.W.; James, J.H.; Sperling, M.; Warner, B.W.; Fischer, J.E.

    1987-01-01

    Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14 C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis

  19. Aetiology of community-acquired neonatal sepsis in low- and middle-income countries

    Directory of Open Access Journals (Sweden)

    Donald Waters

    2011-12-01

    Full Text Available 99% of the approximate 1 million annual neonatal deaths from life-threatening invasive bacterial infections occur in developing countries, at least 50% of which are from home births or community settings. Data concerning aetiology of sepsis in these settings are necessary to inform targeted therapy and devise management guidelines. This review describes and analyses the bacterial aetiology of community-acquired neonatal sepsis in developing countries.

  20. Science review: Mechanisms of impaired adrenal function in sepsis and molecular actions of glucocorticoids

    OpenAIRE

    Prigent, Hélène; Maxime, Virginie; Annane, Djillali

    2004-01-01

    This review describes current knowledge on the mechanisms that underlie glucocorticoid insufficiency in sepsis and the molecular action of glucocorticoids. In patients with severe sepsis, numerous factors predispose to glucocorticoid insufficiency, including drugs, coagulation disorders and inflammatory mediators. These factors may compromise the hypothalamic–pituitary axis (i.e. secondary adrenal insufficiency) or the adrenal glands (i.e. primary adrenal failure), or may impair glucocorticoi...