Bakgrund Årligen drabbas drygt 30 miljoner människor världen över av sepsis, vilket även är den ledande dödsorsaken på intensivvårdsavdelningar i flertalet länder. I Sverige drabbas årligen 40000 personers av sepsis. Sepsis är ett tidskritiskt tillstånd och kan leda till cirkulatorisk svikt, multiorgansvikt och död. Sjuksköterskan har en viktig roll vid omvårdnaden av patienter med sepsis och därför är det viktigt att belysa sjuksköterskans omvårdnadsinsatser samt det professionella ansvaret. Syfte Syftet med litteraturöversikten var att beskriva sjuksköterskans professionella ansvar vid omvårdnad av patienter med sepsis. Metod En begränsad litteraturöversikt genomfördes där aktuella kvalitativa och kvantitativa vetenskapliga forskningsartiklar granskades, bearbetades och analyserades. Resultat Resultat visade på att låg kompetens och låg följsamhet utifrån riktlinjerna för omvårdnad leder till underdiagnostiserade patienter, vilket i förlängningen leder till höga morbiditets- och mortalitetssiffror bland patienter med sepsis, svår sepsis och septisk chock. Tidig identifiering, adekvat behandling och tydlig kommunikation interprofessionellt är av högsta betydelse för att öka överlevnadschanserna för dessa patienter. Slutsats Trots tydliga riktlinjer för omvårdnad framkom det i resultatet att sjuksköterskans låga kompetens och låga följsamhet till riktlinjer inom omvårdnad av patienter med sepsis var en avgörande del i vårdresultatet. För att tillföra denna information till omvårdnadsprofessionen kan fortbildning vara ett förbättringsförslag. Sepsis är ett tidskritiskt tillstånd som bör lyftas inom sjukvården för att mortalitetssiffrorna ska sjunka.

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51–1.72) in multivariable Cox proportional hazards regression analysis. Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

No description available.

Sepsis-induced immunosuppression increases the risk of chronic infection and reduces survival. Myeloid-derived suppressor cells (MDSCs) expand in the bone marrow and spleen during murine polymicrobial sepsis, contributing to immunosuppression. A better understanding of molecular controls of MDSC production is needed to identify treatment targets. We previously reported that miR-21 and miR-181b couple with transcription factor NFI-A to induce MDSCs during murine sepsis. Here, we expand upon these observations by showing that conditional deletion of the Nfia gene in the myeloid lineage precludes MDSC development. NFI-A-deficient Gr1+CD11b+ myeloid cells are not immunosuppressive and differentiate normally into macrophages and dendritic cells. In contrast, ectopically expressed NFI-A prevents differentiation of these immature Gr1+CD11b+ cells, while converting them into MDSCs. In addition, NFI-A-deficient Gr1+CD11b+ cells decreased, and cells transfected with NFI-A increase expression of miR-21 and miR181b. Our results support a myeloid cell loop in which NFI-A and miR-21 and miR-181b sustain Gr1+CD11b+ MDSC-dependent immunosuppression during sepsis.

Serum lactate levels are traditionally interpreted as a marker of tissue hypoxia and often used clinically as an indicator of severity and outcome of sepsis/septic shock. Interestingly, recent studies involving the effects of tumor-derived lactate suggest that lactate itself may have an immunosuppressive effect in its local environment. This finding adds to the recent advances in immunometabolism that shed light on the importance of metabolism and metabolic intermediates in the regulation of innate immune and inflammatory responses in sepsis. In this article, we summarize recent studies, showing that the activation of immune cells requires aerobic glycolytic metabolism and that lactate produced by aerobic glycolysis may play an immunosuppressive role in sepsis.

Objective: To determine whether there was a correlation between induction of polymicrobial sepsis, modulation of tissue Toll-like receptor (TLR) gene, and protein expression and survival outcome. Design: Prospective, randomized animal study. Setting: University medical school research laboratory. Subjects: Age- and weight-matched ICR/HSD mice. Interventions: Sepsis was induced by cecal ligation and puncture (CLP). No-surgery and sham (laparotomy)-operated mice were controls. We also examined tissue TLR2 and TLR4 messenger RNA and TLR4 protein levels in mice treated with an immunomodulator that increases survival in polymicrobial sepsis. In the immunomodulator study, mice were treated with glucan phosphate (50 mg/kg, intraperitoneally) 1 hr before CLP. No-surgery, sham surgery, glucan + no-surgery, sham surgery + glucan, and CLP groups were employed as controls. Measurements and Main Results: Total RNA was isolated from liver, lung, and spleen at 0, 1, 3, 6, 8, and 24 hrs after CLP. TLR gene expression was assessed by reverse transcription-polymerase chain reaction. Tissue TLR4 protein levels were evaluated at 24 hrs by Western blot and immunohistochemistry. CLP sepsis increased (p < .05) liver and lung TLR2 and TLR4 gene expression compared with controls. TLR4 protein concentrations also were increased. Increased TLR2/4 gene and TLR4 protein expression correlated with mortality. Immunoprophylaxis with glucan phosphate increased (p < .001) long-term survival (20% vs. 70%) but inhibited (p < .05) CLP-induced increases in tissue TLR2 and TLR4 messenger RNA expression as well as TLR4 protein expression. Conclusions: Early increases in TLR2/4 gene and TLR4 protein expression correlated with mortality, whereas blunting TLR gene and protein expression correlated with improved long-term survival. This suggests that early up-regulation of tissue TLR2/4 may play a role in the proinflammatory response and pathophysiology of polymicrobial sepsis.

Growing evidence supports the role of transcription factor activation in the pathophysiology of inflammatory disorders, sepsis, ARDS, SIRS, and shock. Kinase mediated phosphorylation of IκBα is a crucial step in the NFκB activation pathway. We investigated IκBα phosphorylation in murine liver and lung extracts after cecal ligation and puncture (CLP) in the presence and absence of a glucan ligand. ICR mice were subjected to CLP. Unoperated and sham-operated mice served as the controls. Glucan phosphate (50 mg/kg) was administered 1 h before or 15 min after CLP. CLP increased hepatic and pulmonary levels of phospho-IκBα by 48-192%. Pre-or post-treatment with glucan phosphate decreased (P < 0.05) tissue phospho-IκBα levels in CLP mice. Phospho-IκBα in the glucan-CLP group were not significantly different from the unoperated controls. To investigate mechanisms we examined IKKβ kinase activity, IκBα phosphorylation and degradation, and NFκB activity in a murine macrophage cell line, J774a.1, treated with LPS (1 μg/mL) and/or glucan phosphate (1 μg/mL) for up to 120 min. The glucan ligand blunted LPS-induced IKKβ kinase activity, phosphorylation and degradation of IκBα, and NFκB nuclear binding activity. The data indicate that one mechanism by which (1→3)-β-D-glucan may alter the response to endotoxin or polymicrobial sepsis involves modulation of IKKβ kinase activity with subsequent decreases in IκBα phosphorylation and NFκB activation.

Background. This study examined the effect of microRNA-125b (miR-125b) on sepsis-induced cardiac dysfunction. Methods. Mouse hearts were transfected with lentivirus expressing miR-125b (LmiR-125b) 7 days before cecal ligation and puncture (CLP)-induced sepsis. Cardiac function was examined by echocardiography before and 6 hours after CLP (n = 6/group). Survival was monitored following CLP-induced sepsis (n = 12/group). Results. LmiR-125b transfection significantly attenuated cardiac dysfunction due to CLP-induced sepsis. Fractional shortening and ejection fraction values were significantly (P <.05) higher in the LmiR-125b-treated CLP group than in the untreated CLP group. Survival outcome in LmiR-125b-transfected septic mice was markedly improved, compared with mice with CLP-induced sepsis. Transfection of LmiR-125b into the heart significantly suppressed the expression of ICAM-1 and VCAM-1, decreased the accumulation of macrophages and neutrophils in the myocardium, and decreased serum levels of tumor necrosis factor a and interleukin 1β by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6)-mediated nuclear factor κB (NF-κB) activation. In addition, sepsis-induced myocardial apoptosis was markedly attenuated by LmiR-125b transfection through suppression of p53, Bax, and Bak1 expression. In vitro transfection of endothelial cells with miR-125b mimics attenuate LPS-induced ICAM-1 and VCAM-1 expression by suppressing TRAF6 and NF-κB activation. Conclusions. Increased myocardial miR-125b expression attenuates sepsis-induced cardiac dysfunction and improves survival. miR-125b may be a target for septic cardiomyopathy.

Mounting evidence supports that sepsis-associated immunosuppression increases mortality. As potential contributors to poor sepsis outcomes, myeloid-derived suppressor cells, which are Gr1+ CD11b+ innate-immune cell progenitors unable to differentiate and possess suppressive activities, expand dramatically in septic mice by a process requiring increased microRNA-21 and microRNA-181b expression. The inhibition of these microRNAs in vivo in septic mice restores Gr1+ CD11b+ cell differentiation and maturation and improves survival. Here, we show that during sepsis-induced generation of myeloid-derived suppressor cells, transcription factor nuclear factor 1 A type represses cyclin-dependent kinase inhibitor p21 to arrest differentiation of Gr1+ CD11b+ cells. Our findings include the following: 1) Gr1+ CD11b+ myeloid cells from late septic mice genetically lacking nuclear factor 1 A type cannot suppress CD4+ T cell proliferation and activation; 2) the reconstitution of nuclear factor 1 A type in microRNA-21 and microRNA-181b-depleted Gr1+ CD11b+ myeloidderived suppressor cells inhibits cyclin-dependent kinase inhibitor p21 and restores the immunesuppressor phenotype; 3) ex vivo nuclear factor 1 A type knockdown in Gr1+ CD11b+ myeloid-derived suppressor cells from late septic mice restores cyclindependent kinase inhibitor p21 expression and promotes monocyte and dendritic cell differentiation; and 4) ectopic nuclear factor 1 A type expression in normal Gr1+ CD11b+ cells generates an immunosuppressive phenotype. We suggest that therapeutically targeting nuclear factor 1 A type during late sepsis might improve survival.

Effective treatment of the acute systemic inflammatory response associated with sepsis is lacking, but likely will require new ways to rebalance dysregulated immune responses. One challenge is that human sepsis often is diagnosed too late to reduce the hyperinflammation of early sepsis. Another is that the sequential response to sepsis inflammation rapidly generates an adaptive and immunosuppressive state, which by epigenetic imprint may last for months or years. Emerging data support that the immunosuppressive phase of sepsis can both directly reprogram gene expression of circulating and tissue cells, and disrupt development and differentiation of myeloid precursor cells into competent immunocytes. We recently reported that adoptive transfer of bone marrow CD34+ cells into mice after sepsis induction by cecal ligation and puncture significantly improves late-sepsis survival by enhancing bacterial clearance through improved neutrophil and macrophage phagocytosis. That study, however, did not examine whether CD34+ transfer can modify noninfectious acute systemic inflammatory responses. Here, we report that CD34+ cell transfer mice that have survived late sepsis also resist lethal lipopolysaccharide (LPS)-induced inflammatory shock (88% lived vs 0% of naive mice). The CD34+ cell-recipient survivor mice administered LPS had globally reduced levels of circulating inflammatory mediators compared with naive mice, but their peritoneal and bone marrow-derived macrophages (BMDMs), unlike those from naïve mice, remained LPS responsive ex vivo. We further found that CD34+ cell transfer into LPS-challenged naïve mice had diminished immunosuppression, as assessed by ex vivo responses of peritoneal and BMDMs to LPS challenge. We conclude that CD34+ cell adoptive transfer rebalances dysregulated immune responses associated with sepsis and endotoxin shock.