Septic Systemic Inflammatory Response Syndrome Research Articles

Role of soluble triggering receptor expressed in myeloid cells-1 in distinguishing SIRS, sepsis, and septic shock in the pediatric intensive care unit

BackgroundResearch into new markers has been intensified for early diagnosis, prognosis, and differentiation of SIRS, sepsis, and septic shock in recent years. This study aimed to investigate the role of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1) and interleukin (IL)-6 in distinguishing between systemic inflammatory response syndrome (SIRS), sepsis, and septic shock in pediatric intensive care unit (PICU) patients. MethodsBetween June 2014 and July 2015, 90 consecutive patients who were treated in the PICU were included in this prospective observational study. Patients were divided into four groups: control (n = 23), SIRS (n = 22), sepsis (n = 23), and septic shock (n = 22). All patients were evaluated for white blood cell (WBC), serum C-reactive protein (CRP), procalcitonin (PCT), IL-6, and sTREM-1 levels at 0, 24, and 72 h of admission. The prognostic evaluations were made using the Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction (PELOD) scores. Patients were evaluated in terms of age, gender, prognosis, pathogen growth in culture, PRISM III and PELOD score, WBC, CRP, PCT, IL-6, and sTREM-1 levels and a comparison was made between groups. ResultsThere was no significant difference between all groups in terms of the 0-, 24-, and 72-h sTREM-1 values (p = 0.761, p = 0.360, and p = 0.822, respectively). CRP and PCT values did not differ between the septic shock, sepsis, and SIRS groups at 0, 24, and 72 h. In the septic shock group, the 0-h IL-6 value was significantly higher than that of the SIRS group (p = 0.025). The 24-h IL-6 value in the septic shock group was significantly higher than the values of the sepsis and SIRS groups (p = 0.048 and p = 0.043, respectively). No significant difference was detected between the septic shock, sepsis, and SIRS groups in terms of IL-6 values at 72 h. ConclusionsTREM-1 is not useful for the diagnosis of infection and for distinguishing between sepsis, septic shock, and SIRS since it does not offer a clear diagnostic value for PICU patients, unlike other reliable markers such as WBC, CRP, and PCT. Elevated IL-6 levels may indicate septic shock in PICU patients. More research on sTREM-1 is needed in this setting.

Plasma procalcitonin concentration in healthy calves and those with septic systemic inflammatory response syndrome

The diagnosis of sepsis in calves is challenging. Blood culture and clinical signs combined with a complete blood count have been used for the diagnosis of sepsis. Recent literature in humans and animal species has been focused on sepsis-specific biomarkers, such as procalcitonin (PCT), that may more accurately and efficiently diagnose sepsis. The aim of this study was to evaluate plasma PCT concentrations in healthy and septic calves. Twenty healthy control calves and 58 sick calves with septic systemic inflammatory response syndrome (SIRS) based on SIRS score and clinical findings were included. Calves with septic SIRS were further divided in septic SIRS survivors (SSS) and non-survivors (SSNS). Plasma PCT concentrations were measured with a commercial ELISA assay for cattle. A receiver operating characteristic curve was used to determine cut-off values and corresponding sensitivity and specificity for the diagnosis of sepsis. Differences in plasma PCT concentration between groups (control vs. SSS vs. SSNS) were evaluated.Plasma PCT concentrations in healthy calves and those with septic SIRS were 33.3pg/mL (0–44.3pg/mL) and 166.5pg/mL (85.9–233.0pg/mL), respectively (P<0.001). The optimal cut-off value to predict septic SIRS was 67.39pg/mL (81.0% sensitivity, 95.0% specificity). Plasma PCT concentrations were 127.4pg/mL (72.2–216.0pg/mL) and 234.3pg/mL (204.5–309.4pg/mL) in the SSS and SSNS subgroups, respectively. Statistically significant differences were found among groups (control vs. SSS and SSNS, P<0.0001; SSS vs. SSNS, P>0.05). These results confirmed an increase in plasma PCT concentrations in calves with septic SIRS, as previously reported in humans and other species.

Retrospective evaluation of circulating thyroid hormones in critically ill dogs with systemic inflammatory response syndrome

Critical illness can be associated with transient alterations in circulating thyroid hormone concentrations, indicating the presence of non-thyroidal illness (NTI). NTI is well described in humans, but there are few reports on its occurrence and prognostic significance in dogs. This retrospective study assessed the occurrence of NTI in a population of dogs with systemic inflammatory response syndrome (SIRS) and investigated its association with disease severity (APPLEfast scores). A total of 41 SIRS dogs were included and were divided by SIRS origin (non-septic SIRS, n = 10; septic SIRS, n = 41) and final outcome (survivors, n = 37; non-survivors, n = 4). Healthy, age-matched dogs (n = 15) were included as controls. Serum thyroid hormone levels including total T3, free T3, total T4, and reverse T3 were measured upon admission. Compared to controls, there were significant changes in serum thyroid hormone concentrations in SIRS dogs, suggesting the presence of NTI. Septic SIRS dogs had higher APPLEfast scores and lower serum thyroid hormones concentrations than those in non-septic SIRS and control dogs. In conclusion, NTI was frequent in dogs with SIRS and may be associated with the presence of sepsis or high illness severity.

Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05).Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.

Plasma levels of F-actin and F:G-actin ratio as potential new biomarkers in patients with septic shock

Objective: To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls.Results: F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay’s lowest detection range (78 ng/ml).Conclusions: F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.

Evaluation of Plasma Procalcitonin Concentrations in Healthy Foals and Foals Affected by Septic Systemic Inflammatory Response Syndrome

The aim of this work was to evaluate procalcitonin (PCT) concentrations in healthy foals and in foals with septic systemic inflammatory response syndrome (SIRS). Plasma PCT concentrations were evaluated in 51 foals, and SIRS scale was calculated. Foals were divided into control group (no septic SIRS criteria met) and septic SIRS group (SIRS score ≥2 plus evidence of sepsis or localized infection). Procalcitonin concentrations were evaluated with a commercial ELISA kit. The data were expressed as mean and standard deviation. A t-test was performed between healthy and septic SIRS groups. A receiver operating characteristic (ROC) curve was carried out. Finally, correlation analysis between PCT concentration and SIRS scale was performed by using Pearson test. The PCT concentrations in control and septic SIRS groups were 30.0 ± 33.1 and 178.9 ± 76.0 pg/mL, respectively. The t-test showed differences between control group and septic SIRS group (P < .0001). A positive linear correlation between PCT concentration and SIRS scale was observed (r = 0.73; r2 = 0.53; P < .0001). The ROC curve was statistically significant (P < .0001), and the best cutoff value to determine septic SIRS was 73.04 pg/mL (87.5% sensitivity, 97.1% specificity, and a likelihood ratio of 30.6). Overall, the results showed an increase in plasma PCT concentrations in septic SIRS foals. A cutoff between control and septic SIRS groups was obtained.

Evaluation of Diagnostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor in Sepsis

Background: Sepsis is one of the most important causes of morbidity and mortality in the intensive care units (ICUs). It is difficult to accurately differentiate sepsis from similar diseases rapidly. Therefore, it becomes critical to identify any biomarker with the ability of differentiation between sepsis and nonsepsis conditions. The urokinase plasminogen activator receptor has been implicated as an important factor in regulation of leukocyte adhesion and migration. Objectives: In this study, we evaluated the value of soluble urokinase plasminogen activator receptor (suPAR), erythrocyte sedimentation (ESR), and C-reactive protein (CRP) serum levels in terms of their value for sepsis diagnosis in ICU patients. Patients and Methods: We enrolled 107 ICU patients; 40 with sepsis, 43 with systemic inflammatory response syndrome, and 24 as control group. Serum soluble urokinase plasminogen activator receptor, ESR, white blood cell (WBC), and CRP levels were measured on the day of admission. Results: The group with sepsis had higher suPAR, ESR, and CRP levels compared with the group with noninfectious systemic inflammatory response syndrome (SIRS) (P = 0.01, 0.00 and 0.00, respectively). CRP concentrations and ESR were higher in the sepsis group than in the non-SIRS group (P = 0.00 and 0.00, respectively). In a receiver-operating characteristic curve analysis, ESR, CRP and suPAR had an area under the curve larger than 0.65 (P = 0.00) in distinguishing between septic and noninfectious SIRS patients. CRP, ESR and suPAR had a sensitivity of 87%, 71% and 66% and a specificity of 59%, 76% and 74% respectively in diagnosing infection in SIRS. Conclusions: The diagnostic values of CRP and ESR were better than suPAR and WBC count in patients with sepsis.

The immune response after stimulation with wall components of gram-positive bacteria and fungi

Although several components of the microbial wall of gram-positive bacteria and fungi possess immunostimulatory properties, their pathogenetic role remains incompletely evaluated. The purpose of this study was to assess the basic immune status of patients susceptible to infections and their capability for cytokine production after stimulation with wall components of gram-positive bacteria and fungi. We measured serum cytokine levels as well as cytokine production after ex vivo lipoteichoic acid (LTA) and mannan stimulation of whole blood. The blood was taken from 10 healthy volunteers, 10 patients with end-stage renal disease (ESRD), 10 patients with diabetes mellitus (DM), and 10 patients on their 2nd day of stay in the Intensive Care Unit (ICU), who suffered from non septic systemic inflammatory response syndrome (SIRS) and had an APACHE II score ≥25. We used 1μg/ml LTA and 100μg/ml mannan for an incubation period of 8h to stimulate 100μl aliquots of whole blood. All patient groups had higher baseline values of TNF-α, IL-6, IL-1β, and IL-10 compared to the control group, but only for ICU patients the difference was statistically significant. The ratio IL-10/IL-6 was found 0.33, 0.22, and 0.96 in healthy persons, ESRD, and DM patients respectively, and 1.32 in ICU patients. In all examined groups, the levels of cytokines significantly increased after stimulation by LTA and mannan, although in severely ill patients this change was considerably smaller, possibly reflecting a state of monocytes’ depression and relative hyporesponsiveness. No significant differences between the LTA and the mannan stimulation were observed.

OP0104 Hypouricemia due to high urate renal excretion in septic systemic inflammatory response syndrome

BackgroundUric Acid (UA) is filtered at the glomeruli and absorbed at the tubule, so only 7-12% of the filtered UA is finally excreted. It has been shown that Serum Uric...

Polymorphic mononuclear neutrophils CD64 index for diagnosis of sepsis in postoperative surgical patients and critically ill patients

Surface neutrophil CD64 expression is upregulated in patients with bacterial infection. As it was suggested that the CD64 index could be used to detect sepsis in hospitalized patients, we questioned whether the CD64 index could discriminate between septic patients and postoperative surgical patients, defined as systemic inflammatory response syndrome (SIRS), both admitted at the intensive care unit (ICU). Furthermore, we wondered whether the CD64 index was an improved diagnostic compared to standard assays used at the laboratory. For this, outclinic (OC) patients were included as controls. The Leuko64™ assay was used to determine the CD64 index in residual EDTA blood samples from selected septic patients (n=25), SIRS patients (n=19), and OC patients (n=24). Additionally, WBC count, neutrophilic and eosinophilic granulocyte count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured simultaneously. The CD64 index was higher in septic patients compared to both the SIRS and OC group (p<0.0001). In addition, the WBC count, neutrophil count, ESR and CRP were also higher in septic patients than the OC group (p<0.0001). However, only the WBC count, eosinopenia, and ESR were comparable between the SIRS and the sepsis group and proved to be discriminative to the OC group (p<0.05). The CD64 index demonstrated higher sensitivity and specificity than CRP, WBC count, neutrophilic and eosinophilic granulocyte count, and ESR. A high CD64 index was found in septic intensive care patients, while a low CD64 index was observed in OC and SIRS patients, demonstrating that the CD64 index can be used for routine diagnostics in the ICU setting.

Application of skin conductance measuring to assist pain therapy

Objectives: The aim of this study was to investigate the longitudinal changes of temperature variability using wavelets transformation of the continuously monitored temperature signal, in a mixed population of critically ill patients, during the course of a suspected intensive care unit–acquired infection. Methods: Continuous temperature recordings were performed in 12 patients with ventilator-associated pneumonia, 10 with bloodstream infections, and 7 with systemic inflammatory response syndrome (SIRS). Ten patients developed septic shock, and 12 were considered having sepsis. Temperature monitoring was performed with a thermistor sensor (Datalogger Spectrum 1000; Veriteq Instruments, Richmond, BC, Canada), with a sampling frequency of 1 sample per 10 seconds. Continuous wavelet transformation was applied to the temperature signal, aiming at decomposing it to different frequency components (0.008-0.02 and 0.02-0.05 Hz, indicating metabolic and neurogenic inputs upon local temperature control, respectively) during different time scales, using software available from MATLAB. Different features indicating variability of the signal, such as wavelet coefficients, wavelet, and sample entropy measures per frequency band, were computed and correlated with daily measured specific organ failure assessment score of severity of illness. Multiple analyses of variance and cluster analysis using Mahalanobis distance evaluated differences between groups of patients (SIRS, sepsis, and septic shock). Multiple regression analyses assessed whether different features from continuous wavelet transformation were independent predictors of specific organ failure assessment score and development of septic shock. Results: Average sample entropy of the whole signal was significantly increased in patients with SIRS vs sepsis and septic shock (3.7 ± 0.2 vs 2.8 ± 0.12 vs 2.2 ± 0.18, P b .001, respectively, for all comparisons). Entropy/metabolic band was significantly increased in the SIRS group (0.07 ± 0.002) related to septic shock group (0.02 ± 0.0016, P b .001). The percentage of cross-correlation greater than 0.95 between 30-second distant time slots was 0.85 vs 0.05 in patients with septic shock vs SIRS (P b .001), indicating more steady and periodic behavior of temperature during severe infection. Entropy/metabolic band and crosscorrelation between adjacent timeslots proved to be independent predictors of severity of illness (β slope = −1.087, P = .022 and .88 and P = .013, respectively). Conclusions: Reduced variability of temperature fluctuations seems to correlate with severity of illness, reflecting different thermoregulatory mechanisms, and can be of prognostic value in patients with systemic inflammation.

Temperature variability analysis using wavelets in critically ill patients during systemic inflammation

Objectives: The aim of this study was to investigate the longitudinal changes of temperature variability using wavelets transformation of the continuously monitored temperature signal, in a mixed population of critically ill patients, during the course of a suspected intensive care unit–acquired infection. Methods: Continuous temperature recordings were performed in 12 patients with ventilator-associated pneumonia, 10 with bloodstream infections, and 7 with systemic inflammatory response syndrome (SIRS). Ten patients developed septic shock, and 12 were considered having sepsis. Temperature monitoring was performed with a thermistor sensor (Datalogger Spectrum 1000; Veriteq Instruments, Richmond, BC, Canada), with a sampling frequency of 1 sample per 10 seconds. Continuous wavelet transformation was applied to the temperature signal, aiming at decomposing it to different frequency components (0.008-0.02 and 0.02-0.05 Hz, indicating metabolic and neurogenic inputs upon local temperature control, respectively) during different time scales, using software available from MATLAB. Different features indicating variability of the signal, such as wavelet coefficients, wavelet, and sample entropy measures per frequency band, were computed and correlated with daily measured specific organ failure assessment score of severity of illness. Multiple analyses of variance and cluster analysis using Mahalanobis distance evaluated differences between groups of patients (SIRS, sepsis, and septic shock). Multiple regression analyses assessed whether different features from continuous wavelet transformation were independent predictors of specific organ failure assessment score and development of septic shock. Results: Average sample entropy of the whole signal was significantly increased in patients with SIRS vs sepsis and septic shock (3.7 ± 0.2 vs 2.8 ± 0.12 vs 2.2 ± 0.18, P b .001, respectively, for all comparisons). Entropy/metabolic band was significantly increased in the SIRS group (0.07 ± 0.002) related to septic shock group (0.02 ± 0.0016, P b .001). The percentage of cross-correlation greater than 0.95 between 30-second distant time slots was 0.85 vs 0.05 in patients with septic shock vs SIRS (P b .001), indicating more steady and periodic behavior of temperature during severe infection. Entropy/metabolic band and crosscorrelation between adjacent timeslots proved to be independent predictors of severity of illness (β slope = −1.087, P = .022 and .88 and P = .013, respectively). Conclusions: Reduced variability of temperature fluctuations seems to correlate with severity of illness, reflecting different thermoregulatory mechanisms, and can be of prognostic value in patients with systemic inflammation.

Selenoprotein P, Rather than Glutathione Peroxidase, as a Potential Marker of Septic Shock and Related Syndromes

Background/Aims: Oxidative stress is involved in sepsis-related endothelium dysfunction. Selenoprotein-P (Sel-P), the main plasma selenoprotein, may have high antioxidant potential, and binds to endothelium. We hypothesize that, in septic shock, and similar syndromes such as systemic inflammatory response syndrome (SIRS), Sel-P binds massively to endothelium, causing a drop in Sel-P plasma concentration. Methods: Plasma Se, Sel-P and albumin concentrations, and glutathione peroxidase (GPx) activity were measured in patients with septic shock and SIRS with organ failure (S group, n = 7 and n = 3, respectively) admitted to the intensive care unit (ICU) and compared to non-SIRS patients (NS group, n = 11) and healthy volunteers (HV group, n = 7). Results: On ICU admission, plasma Sel-P concentrations were 70% lower in the S group than in the other groups [15 (10–26) vs. 44 (29–71) and 50 (45–53) nmol/l] and were lower in nonsurviving septic-shock patients. GPx activity did not differ between groups. Sel-P was significantly lower before ICU death in the 3 deceased patients of the S group (septic shock) than in the 3 patients of the non-SIRS group. Conclusions: Early decrease in Sel-P plasma concentrations was specifically observed in septic shock and was similar in SIRS patients whereas GPx activity remained unchanged. Further studies are needed to determine whether Sel-P can be an early marker of septic shock linked to microvascular injury.

Sepsis is Characterized by the Increases in Percentages of Circulating CD4+CD25+ Regulatory T Cells and Plasma Levels of Soluble CD25

The function of immune system is to protect hosts from invading microorganisms by destroying infected cells while minimizing damage to tissues. Among immune cells, CD4(+)CD25(+) regulatory T cells (Treg cells) control immune responses by limiting infectious processes. However, it remains unclear whether Treg cells are induced in systemic inflammatory response syndrome (SIRS) or infectious SIRS (i.e. sepsis). SIRS and sepsis are associated with stressful inflammatory conditions. We therefore measured CD25(+) T cells and circulating CD4(+) T cells, along with plasma levels of CD25, interleukin (IL)-6, and IL-10, in 20 septic patients (64 +/- 11 years), 16 SIRS patients (59 +/- 16 years), and control subjects: 13 elderly (60 +/- 16 years) and 14 young volunteers (28 +/- 3 years). Septic patients (23.3 +/- 11.8%, p < 0.01) showed significantly higher percentages of CD25(+) cells among CD4(+) T cells (i.e. Treg cells) than did either young (10.6 +/- 3.7%) or elderly volunteers (11.1 +/- 3.8%). The percentages of Treg cells in septic patients were higher than those in SIRS patients (12.4 +/- 6.9%, p < 0.01). Moreover, plasma levels of soluble CD25 were significantly higher in septic patients, compared to the levels in SIRS patients or volunteers (p < 0.01). No significant difference in plasma levels of IL-6 or IL-10 was found between septic patients and SIRS patients. Thus, sepsis is associated with the increased percentages of Treg cells and elevated plasma level of soluble CD25. The elevation of these parameters might be a useful marker of infections in SIRS.

Coagulation and Complement Protein Differences Between Septic and Uninfected Systemic Inflammatory Response Syndrome Patients

Systemic inflammatory response syndrome (SIRS) represents a host response to various insults. Recent advances have demonstrated an interconnection between inflammation, complement, and coagulation. This experiment was designed to evaluate differences in plasma protein profiles between clinically identical patients: septic versus uninfected SIRS patients, prior to clinical diagnosis of infection. Patients admitted to an intensive care unit of a major university, meeting two of four SIRS criteria were followed prospectively for development of sepsis. Plasma samples were collected daily and divided into two groups: a preseptic group that subsequently developed sepsis and a SIRS group that remained uninfected. Protein profiling was accomplished by three-dimensional liquid chromatography fractionation with electrospray ion trap mass spectrometry after immunodepletion of abundant proteins and a trypsin digest. Spectra peaks were identified using Agilent Technologies Spectrum Mill Workbench software. Relevance to biologic pathways was analyzed and statistical significance determined with DAVID 2.1 available at the National Institutes of Health. A total of 134 unique proteins were significantly different between groups. Thirty-two of these (23.5%) mapped to the complement and coagulation cascade (KEGG), 10 (7.5%) mapped to classic complement pathway; 11 (8.2%) mapped to complement pathway, and 8 (6.0%) mapped to lectin binding complement pathway (Biocarta). These pathways were all significantly (p<0.0001) over-represented in sepsis patients compared to SIRS-only patients. Using novel mass spectrometry methodology, we were able to demonstrate differential protein profiles in septic versus uninfected SIRS patients prior to clinical diagnosis of sepsis.

128: Decreased lysophosphatidylcholine levels are associated with sepsis compared to uninfected inflammation prior to onset of sepsis

Introduction: Systemic inflammatory response syndrome (SIRS) represents the host response to various insults and when associated with infection is referred to as sepsis. Recent studies suggest that phospholipids play a significant role in the pathogenesis of sepsis, but their role in uninfected systemic inflammation is unclear. Lysophosphatidylcholine (LPC) has been shown to be decreased in sepsis compared to healthy controls. This study evaluated differences in phospholipids between septic and uninfected SIRS patients, prior to the clinical diagnosis of sepsis.

Risk factors of disseminated intravascular coagulation in septic systemic inflammatory response syndrome in nursing home residents

Aims: Disseminated intravascular coagulation syndrome (DIC) is a serious complication in elderly patients with systemic inflammatory response syndrome (SIRS). We investigated whether the clinically relevant parameters of atherosclerosis, nutrition and cellular immunity are determining factors for DIC in septic SIRS patients or not. Patients and methods: Forty-four subjects aged 65 years or over were enrolled, all of whom had bacterial sepsis and a high concentration of C-reactive protein (≥ 15.0 mg/dL). Subjects were given gabexate mesilate (GM) following diagnosis of DIC. They were divided into the following groups: N-DIC, subjects with SIRS but not DIC (n = 22); DIC-A, subjects with SIRS and DIC who survived through treatment with GM (n = 6); and DIC-D, subjects who had SIRS and DIC and died despite treatment with GM (n = 16). Results: Subjects with a low hemoglobin or serum albumin concentration, and atrial fibrillation at admission had a significantly high incidence of DIC, which was not high in subjects with myocardial ischemia, past history of overt cerebral infarctions or periventricular lucency. There was no difference in hemoglobin concentration between DIC-A and DIC-D. Differences in increases in CD11b- and CD14-positive mononuclear cells between DIC and N-DIC subjects were not significant. Post-mortem examinations showed that the ratio of the width of the thoracic aorta to that of the abdominal aorta was significantly higher for DIC-D than DIC-A. Conclusion: Nutritional disorders and irregularity in aortic blood flow are significant risks of DIC. Treatment with GM alone is not sufficient to achieve survival in patients with DIC and SIRS.

Gastroduodenal perfusion and mortality in mechanical ventilation-dependent patients with systemic inflammatory response syndrome.

The role of gastrointestinal blood flow determination in predicting mortality is not known. We tested the hypothesis that when mechanical ventilation-dependent (MVD) patients with systemic inflammatory response syndrome (SIRS) develop a significant reduction in gastroduodenal blood flow, high mortality will ensue. The design was a prospective, observational study at the intensive care unit (study patients) and outpatient endoscopy suite (controls) of a tertiary care Veterans Affairs Hospital. There were 6 study patients and 10 control subjects. Interventions were endoscopic reflectance spectrophotometry recorded indexes of gastroduodenal mucosal oxygen saturation (ISO2) and hemoglobin concentration (IHB). Data for Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were gathered. All study patients had septic SIRS at enrollment. Gastroduodenal blood flow measurements ranged from 32 to 55% (ISO2) and from 42 to 51% (IHB) of those in control subjects. The significant hypoperfusion upgraded diagnosis to severe sepsis. The APACHE II score of 16.8 +/- 2.8 (mean +/- SE) predicted approximately 25% mortality. Observed in-hospital mortality was 83%. Our study confirmed that MVD patients with severe sepsis have a significant impairment of gastroduodenal blood flow. Such a dramatic reduction is associated with a grave prognosis. The impact of these measurements on physicians' predictions of the likelihood of survival in patients receiving intensive care deserves to be assessed.

Western blot analysis of bile or intestinal fluid from patients with septic shock or systemic inflammatory response syndrome, using antibodies to TNF‐α, IL‐1α and IL‐1β

Septic shock or systemic inflammatory response syndrome (SIRS) often develops in patients following burns, traumatic injury, surgery or biliary obstruction. Although the inflammatory cytokines TNF-alpha and IL-1 have been strongly implicated in the development of these syndromes, treatment of patients by the systemic administration of inhibitors of TNF-alpha or IL-1 has shown limited effectiveness. Recent reports suggest that septic shock may be perpetuated by inflammatory cytokines secreted by the liver in response to bacterial translocation resulting from cytokine-induced gastrointestinal damage. The present study sought to demonstrate the presence of high levels of inflammatory cytokines in the bile or small intestine of patients suffering from septic shock or SIRS, with a view to the development of strategies for the reduction of gastrointestinal damage through intraduodenal administration of cytokine inhibitors. Western blot analysis of human bile or intestinal fluid using anti-TNF-alpha antibodies resulted in the detection of a number of bands in samples from patients with septic shock or SIRS. However, these proteins differed antigenically from human recombinant TNF-alpha (rTNF-alpha) and showed no activity in a biological assay for TNF-alpha. Antibodies to IL-1 alpha and IL-1 beta detected several strong bands, some of which appeared to be identical to recombinant IL-1 alpha and IL-1 beta. It is concluded that proteins resembling several known inflammatory cytokines are present in the bile and intestine of septic shock patients, but it is suggested that further work is required to determine the nature and function of these molecules.