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PubMed2006

[Diagnosis and therapy of sepsis. Guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine].

A recent survey conducted by the publicly funded Competence Network Sepsis (SepNet) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approximately 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approximately 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organization of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to the requirements of the Working Group of Scientific Medical Societies (AWMF).

Delivery of Health Care, Integrated↗
PubMed2006

[Diagnosis and therapy of sepsis: guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine].

A recent survey conducted by the publicly funded Competence Network Sepsis (SepNet) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approximately 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approximately 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organization of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to the requirements of the Working Group of Scientific Medical Societies (AWMF).

Anti-Bacterial Agents↗
PubMed2004

Severity of sepsis alters the effects of superoxide anion inhibition in a rat sepsis model.

Previous analysis showed that selective inhibitors of five different host inflammatory mediators administered for sepsis, although beneficial with severe sepsis and high-control mortality rates, were ineffective or harmful with less severe sepsis. We hypothesized that severity of sepsis would also influence inhibition of superoxide anion, another inflammatory mediator. To test this, 6-h infusions of M40401, a selective SOD mimetic, or placebo were given to antibiotic-treated rats (n=547) starting 3 h after challenge with differing doses of intravenous Escherichia coli designed to produce low- or high-control mortality rates. There was a positive and significant (P=0.0008) relationship between the efficacy of M40401 on survival rate and control mortality rates. M40401 increased or decreased the log (odds ratio of survival) (means +/- SE), dependent on whether control mortality rates were greater or less than the median (66%) (+0.19 +/- 0.12 vs. -0.25 +/- 0.10, P=0.01). In a subset of animals examined (n=152) at 9 h after E. coli challenge, M40401 increased (mean effect +/- SE compared with control) mean arterial blood pressure (8 +/- 5 mmHg) and decreased platelets (-37 +/- 22 cells x 10(3)/ml) with high-control mortality rates but had opposing effects on each parameter (-3 +/- 3 mmHg and 28 +/- 19 cells x 10(3)/ml, respectively) with low rates (P < or = 0.05 for the differing effects of M40401 on each parameter with high- vs. low-control mortality rates). A metaregression analysis of published preclinical sepsis studies testing SOD preparations and SOD mimetics showed that most (16 of 18) had control mortality rates >66%. However, across experiments from published studies, these agents were less beneficial as control mortality rate decreased (P=0.03) in a relationship not altered (P=not significant) by other variables associated with septic challenge or regimen of treatment and which was similar, compared with experiments with M40401 (P=not significant). Thus, in these preclinical sepsis models, possibly related to divergent effects on vascular function, inhibition of superoxide anion improved survival with more severe sepsis and high-control mortality rates but was less effective or harmful with less severe sepsis. Extrapolated clinically, inhibition of superoxide anion may be most efficacious in septic patients with severe sepsis and a high risk of death.

Animals↗
PubMed1994

Intravascular catheter associated sepsis: a common problem. The Australian Study on Intravascular Catheter Associated Sepsis.

OBJECTIVE: To estimate the number of episodes of intravascular catheter associated sepsis that occur in Australia per year. DESIGN AND SETTING: Data were collected from 15 Australian hospitals (mainly tertiary referral hospitals). All positive results of blood cultures were followed up and the primary sepsis site identified and recorded. The average study period was 1.2 years. RESULTS: Eight hundred and nine episodes of systemic sepsis associated with intravascular catheters were identified from 4957 separate episodes of bacteraemia or fungaemia. Of those in which the catheter site was known, there were 491 episodes of sepsis associated with central vein catheters and 233 with peripheral vein catheters. Systemic sepsis with peripheral vein catheters occurred with 0.36 of every 1000 catheters purchased, but with central vein catheters it was 23 episodes per 1000 catheters (relative risk, 64; 95% confidence interval, 54-76). In these hospitals, 8.2 episodes of intravascular catheter associated sepsis occurred annually per 100 beds and 1.5 episodes per 1000 admissions. From these figures, at least 3000 cases of intravascular sepsis may occur per year in Australia. CONCLUSIONS: Intravascular catheter sepsis is common. Central vein catheters cause more sepsis than peripheral vein catheters. With the greater use of catheters this problem is likely to increase.

Australia↗
PubMed2001

Glycine attenuates hepatocellular depression during early sepsis and reduces sepsis-induced mortality.

OBJECTIVES: To determine whether administration of glycine, a nonessential amino acid, early after the onset of polymicrobial sepsis has any beneficial effects on hepatocellular function and the survivability of septic animals and, if so, whether the beneficial effects of glycine are associated with down-regulation of proinflammatory cytokine tumor necrosis factor-alpha production. DESIGN: Prospective, controlled, and randomized animal study. SETTING: A university research laboratory. SUBJECTS: Male adult rats were subjected to polymicrobial sepsis by cecal ligation and puncture or sham operation followed by the administration of normal saline solution. MEASUREMENTS AND MAIN RESULTS: At 1 hr after cecal ligation and puncture, glycine (0.6 mmol/kg) or vehicle (normal saline solution) was administered intravenously over 15 mins. At 5 hrs after cecal ligation and puncture (i.e., early stage of sepsis), hepatocellular function (i.e., the maximal velocity and efficiency of in vivo indocyanine green clearance) was determined and hepatocyte injury was assessed by measuring plasma concentrations of alpha-gluthathione S-transferase. Serum tumor necrosis factor-alpha was measured by enzyme-linked immunosorbent assay. In additional animals, the necrotic cecum was excised at 20 hrs after cecal ligation and puncture, the peritoneal cavity was irrigated with saline, and the midline incision was closed in layers. Mortality was monitored for 10 days thereafter. The results indicate that hepatocellular function was depressed in the early stage of sepsis (i.e., 5 hrs after cecal ligation and puncture) as indicated by significant decreases in both maximal velocity and transport efficiency of in vivo indocyanine green clearance. Plasma concentrations of alpha-gluthathione S-transferase and tumor necrosis factor-alpha were elevated significantly at that interval after cecal ligation and puncture. Administration of glycine 1 hr after cecal ligation and puncture, however, increased maximal velocity and maximal efficiency by 60% and 101% (p <.05), respectively. Glycine administration in septic animals decreased alpha-gluthathione S-transferase and tumor necrosis factor-alpha by 43% and 80% (p <.05). In addition, glycine treatment decreased the mortality rate from 50% to 0% (p <.05) at 10 days after cecal ligation and puncture and cecal excision. CONCLUSIONS: It appears that the beneficial effect of glycine on hepatocyte function and integrity in sepsis may be mediated via down-regulation of tumor necrosis factor-alpha. Because administration of glycine attenuated hepatocellular depression and injury during early sepsis and decreased sepsis-induced mortality rates, this amino acid appears to be a useful adjunct for maintaining cellular functions and preventing lethality from polymicrobial sepsis.

Analysis of Variance↗
PubMedDate not supplied

Shock in children with gram-negative bacillary sepsis and Haemophilus influenzae type b sepsis.

To study the incidence of shock in children in association with gram-negative bacillary (GNB) sepsis and Haemophilus influenzae type b sepsis, we reviewed all episodes of septicemia with those organisms in a 10-month period. GNB were isolated from 10.95% and H. influenzae b from 13.8% of the patients whose blood cultures yielded bacteria. Shock occurred in 12.5% of patients with sepsis caused by GNB and in 10.3% of those with H. influenzae b sepsis. Shock occurred more frequently in patients with H. influenzae b sepsis with meningitis (20.6%) and more commonly in those who had GNB sepsis without meningeal involvement (11.4%). GNB sepsis was associated with severe shock and caused death of three of the four patients. Only one of the five patients with shock caused by H. influenzae b had severe shock and died. The good outcome of patients with sepsis and shock caused by H. influenzae may be related to the health status before illness and prompt appropriate antibiotic therapy.

Gram-Negative Bacteria↗
PubMed2006

TLR2, TLR4, CD14, CD11B, and CD11C expressions on monocytes surface and cytokine production in patients with sepsis, severe sepsis, and septic shock.

Bacterial recognition and induced cellular activation are fundamental for the host control of infection, yet the limit between protective and harmful response is still inexact. Forty-one patients were enrolled in this study: 14 with sepsis, 12 with severe sepsis, and 15 with septic shock. Seventeen healthy volunteers (HV) were included as control. The expression of TLR2, TLR4, CD14, CD11b, and CD11c was analyzed on monocytes surface in whole blood. sCD14 was measured in serum, and TNF-alpha, IL-6, and IL-10 cytokine levels were measured in PBMC supernatants after LPS, IL-1beta, and TNF-alpha stimuli by ELISA. An increase in sCD14 and a decreased mCD14 were found in patients as compared with HV (P < 0.001). However, no differences in the expression of TLR2, TLR4, and CD11c were found among the groups. A trend toward differential expression of CD11b was observed, with higher values found in patients with sepsis as compared with HV. A negative regulation of the inflammatory cytokine production was observed in patients with severe sepsis and shock septic in relation to sepsis and HV, regardless of the stimulus. No significant difference in IL-10 production was found among the groups. In this study, we show that the inflammatory response is associated with the continuum of clinical manifestations of sepsis, with a strong inflammatory response in the early phase (sepsis) and a refractory picture in the late phases (severe sepsis and septic shock). Correlation between cell surface receptors and cytokine production after IL-1beta and TNF-alpha stimuli and the observation of a single and same standard response with the different stimulus suggest a pattern of immunology response that is not dependent only on the expression of the evaluated receptors and that is likely to have a regulation in the intracellular signaling pathways.

Antigens, CD↗
PubMed2005

Interleukin-10 haplotype associated with increased mortality in critically ill patients with sepsis from pneumonia but not in patients with extrapulmonary sepsis.

STUDY OBJECTIVE: To test the hypothesis that haplotypes of the interleukin (IL)-10 gene are associated with clinical outcomes, comparing critically ill patients with sepsis from pneumonia vs those with extrapulmonary sepsis. DESIGN: Genetic association study. SETTING: Medical/surgical ICUs in a tertiary-care, university-affiliated teaching hospital. PATIENTS: Of 550 white patients with sepsis, 158 had pneumonia as the principle cause of their sepsis and 392 had an extrapulmonary source of sepsis. MEASUREMENTS: Haplotypes of the IL-10 gene were defined by measurement of haplotype tag single-nucleotide polymorphisms (SNPs). Primary outcome was 28-day survival. Secondary outcomes were days alive and free of organ dysfunction. RESULTS: Three SNPs in the IL-10 gene (-592 C/A, +734 G/T, and +3367 G/A) identified four major haplotypes: CGG, AGG, CTA, and CTG. Patients with pneumonia who carried one or two copies of the CGG haplotype had greater 28-day mortality (51.4%) than patients who did not carry this haplotype (29.1%, p = 0.007). Carriers of CGG had significantly more cardiovascular dysfunction (and use of vasopressors), renal dysfunction (and requirement of dialysis), hepatic dysfunction, and hematologic dysfunction (p < 0.05 in each case). In contrast, in patients with an extrapulmonary source of infection there was no significant association of the CGG haplotype (or any measured IL-10 genotype) with 28-day mortality or organ dysfunction. CONCLUSIONS: The IL-10 haplotype - 592C/734G/3367G is associated with increased mortality and organ dysfunction in critically ill patients with pulmonary sepsis but not in similarly ill patients with extrapulmonary sepsis. Therefore, polymorphisms within the IL-10 gene may be predictors of outcome in patients with sepsis from pneumonia.

Adolescent↗
PubMed1989

Vaginal flora of women admitted to hospital with signs of sepsis following normal delivery, cesarean section or abortion. The Puerperal Sepsis Study Group.

The microbial flora of the genital tract of 95 women who developed clinical signs of infection within 48 hr of vaginal delivery, Cesarean section delivery or abortion were compared with 111 women who delivered at the same hospital during the same time period but who showed no signs of sepsis. While there were no significant differences in the prevalence of most organisms in the lower genital tract of women with and without sepsis, there was evidence of a higher prevalence of gonococcal, chlamydial and anaerobic infection in the former. Gonococci were isolated from over 20 percent of untreated women with sepsis, more than three times the prevalence in controls. A third of the isolates were penicillinase-producing and another third showed in vitro resistance to penicillin. Chlamydial antigen was detected in 16-20 percent of women with sepsis following vaginal delivery or abortion, compared with 6 percent of controls. Neither gonococcal nor chlamydial infections were significantly associated with sepsis following Cesarean section delivery. Clue cells, indicative of G. vaginalis infection were noted in 20 percent of patients with sepsis compared with 7 percent of controls while amongst the other anaerobes only pigment producing Bacteroides were associated with sepsis. These findings suggest that antepartum investigations for clue cells, chlamydial antigen, gonococci and pigment producing anaerobes may identify patients most at risk from obstetric sepsis in Harare, and identify those for whom prophylactic administration of antibiotics may be of benefit.

Cross-Sectional Studies↗
PubMed1994

Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial. BN 52021 Sepsis Study Group.

OBJECTIVE: To evaluate the safety and efficacy of a natural platelet-activating factor receptor antagonist, BN 52021 (Ginkgolide B), in the treatment of patients with sepsis syndrome. DESIGN: Prospective, randomized, placebo-controlled, double-blind, phase III, multicenter clinical trial. SETTING: Twenty-one academic medical center intensive care units in France. PATIENTS: Two hundred sixty-two patients with sepsis syndrome who received standard supportive care and antimicrobial therapy, in addition to the administration of platelet-activating factor receptor antagonist or placebo. INTERVENTIONS: Patients received either a 120-mg dose of platelet-activating factor receptor antagonist intravenously every 12 hrs over a 4-day period or placebo. MAIN OUTCOME MEASUREMENTS: All patients were evaluated for 28-day, all-cause mortality. RESULTS: The 28-day mortality rate was 51% for the placebo group and 42% for the platelet-activating factor receptor antagonist group (p = .17). However, the efficacy of platelet-activating factor receptor antagonist was significantly greater in patients with Gram-negative sepsis (test for interaction, p = .03). In a separate analysis of patients with and without Gram-negative sepsis, the 28-day mortality rate was 57% for the patients receiving placebo (30 deaths of 53 patients) and 33% for patients receiving platelet-activating factor receptor antagonist (22 deaths of 67 patients; p = .01). Platelet-activating factor receptor antagonist also significantly (p = .01) reduced the mortality rate among patients with Gram-negative sepsis who were in shock at entry into the study (mortality rate was 65% for placebo vs. 37% for platelet-activating factor receptor antagonist) and among patients > 60 yrs of age (mortality rate was 74% for placebo vs. 31% for platelet-activating factor receptor antagonist). A Cox proportional-hazards model identified five independent prognostic factors: a) adequacy of antibiotic therapy; b) severity of illness; c) renal failure; d) hematologic failure; and e) hepatic failure at study entry. When the Gram-negative sepsis population was stratified by age and these five prognostic factors were controlled for, the relative risk of death of the platelet-activating factor receptor antagonist group was 0.61 (0.34 to 1.08, 95% confidence interval; p = .09). This risk corresponds with an adjusted reduction in mortality rate of 39% for patients receiving platelet-activating factor receptor antagonist. No differences in mortality rates were found between the placebo and the platelet-activating factor receptor antagonist groups in the absence of Gram-negative sepsis. There were no differences in adverse events between the placebo and the treated groups. CONCLUSION: The studied platelet-activating factor receptor antagonist (BN 52021) seems to be a safe and promising treatment for patients with severe Gram-negative sepsis.

APACHE↗
PubMed2002

Lectin binding patterns of alveolar epithelium and subepithelial seromucous glands of the bronchi in sepsis and controls--an approach to characterize the non-specific immunological response of the human lung to sepsis.

A delayed or deficient immunological protection as well as an overstimulation of the mucosal immune system may act as possible additional promoters of sepsis-induced lung injury in patients suffering from a severe septic condition. Lectin-binding patterns in pulmonary tissue samples obtained at autopsy from septic patients and control individuals were studied using 11 carbohydrate-specific lectins (Con A, UEA, GSA I, GSA II, MPA, PNA, Jac, WGA, MAA, LPA, and SNA). There were no differences in the secretory product of serous parts of bronchial glands detectable in the two study groups, whereas lectin binding patterns of alveolar epithelium and mucous parts of subepithelial seromucous glands were different in sepsis cases when compared to controls. Apart from differences in binding sites for alpha-mannose, N-acetyl-neuraminic acid and alpha-(2-6)-galactose (as detected by different expression for Con A, MAA and SNA) in the two study groups, the main finding was that no binding sites for alpha-N-acetyl-galactosamine (as investigated by MPA immunoreactivity) could be detected on alveolar epithelial cells and mucous parts of subepithelial seromucous glands in sepsis cases in contrast to the presence of such binding sites in the control cases. We hypothesize that the finding of an altered secretory product of alveolar epithelial cells and bronchial glands in sepsis may be a result of specific carbohydrate deprivation or consumption, respectively, possibly due to direct bacterial effects or pathogenetic events in response to bacterial toxins during the complex cascade of the host's systemic inflammatory response in sepsis. The altered type of mucus glycoprotein physiologically secreted by alveolar epithelium and mucous parts of subepithelial seromucous glands of the bronchi with subsequent loss of a considerable proportion of protection of the mucosal barrier in sepsis may play an important additional role in the development of sepsis-induced lung injury.

Adult↗
PubMed2004

[Diagnosis of sepsis, severe sepsis and septic shock].

Consensual and precise definitions. Sepsis is composed of a suspected or documented infection associated with at least 2 SIRS criteria (systemic inflammatory response syndrome). Severe sepsis is sepsis with arterial hypotension and failure of one or several organs following the reduction in tIssue perfusion. Septic shock is a severe sepsis, the hypotension of which is refractory to volemic expansion. From an epidemiological point of view. Over the past two decades, its incidence is on the increase. Mortality varies from 25 to 80% of cases and sepsis remains the first cause of death in intensive care. The elements of diagnosis. The initial clinical signs are those of an infection and the port of entry and microbiological proof must be systematically researched before the appearance of a drop in blood pressure with hemodynamic impact on the various organs and hence their possible failure. The biological abnormalities observed depend on the deficient organ(s); hyperlactatemia is a good marker of visceral hypoperfusion. The sepsis risk factors. Any situation enhancing immunodepression is a risk factor for sepsis. Factors of virulence of the micro-organisms also intervene and, in cases of fungal infection, inherent risk factors. Genetic susceptibility probably intervenes, genetic variability playing either a protective or a deleterious role (the interest of Toll-like receptors).

Age Factors↗
PubMed1999

Sepsis, severe sepsis and septic shock in paediatric multiple organ dysfunction syndrome.

OBJECTIVES: To determine the association between severity of sepsis with outcome and severity of illness in children with multiple organ dysfunction syndrome (MODS). MATERIALS: Four hundred and ninety-five consecutive paediatric intensive care unit (PICU) admissions were analysed. multiple organ dysfunction syndrome was defined as simultaneous dysfunction of >/= 2 organ system and sepsis by the American College of Chest Physicians and Society of Critical Care Medicine Consensus Conference definition. RESULTS: Eighty-four patients developed MODS. The incidence of sepsis, severe sepsis and septic shock in these patients was 10.7%, 23.8% and 17.9%, respectively. Worsening categories of sepsis were associated with: (1) a higher mean admission Paediatric Risk of Mortality (PRISM II): 36.6 +/- 25.9, 56.8 +/- 32.1 and 73.6 +/- 28.5%, respectively (P = 0. 005), (2) a larger number of organ dysfunctions: mean MODS index of 37%, 46% and 58%, respectively (P = 0.007), and (3) a higher mortality: 22.2%, 65% and 80%, respectively (P = 0.03). CONCLUSION: Presence of sepsis, severe sepsis and septic shock was associated with an increasing severity of illness, increased number of organ dysfunctions and a distinct risk of mortality among critically ill children.

Child, Preschool↗