interleukin-8 and Critical-Illness

Pneumonia is a very common admission diagnosis of critically ill patients. Patients with severe episodes of pneumonia are at risk for development of the systemic inflammatory response syndrome, which is known to induce the production of proinflammatory cytokines, such as interleukins (ILs) and tumor necrosis factor alpha (TNF-alpha). This response subsequently triggers activation of anti-inflammatory cytokine production and specific soluble cytokine receptors. Lung cell apoptosis can be stimulated or inhibited by different cytokines and/or cell signals. Some of these mediators can be proapoptotic or antiapoptotic. This article discusses the clinical implications of the systemic response to pneumonia in the critically ill patient.

Topics: Bronchoalveolar Lavage Fluid; Critical Illness; Cytokines; Disease Progression; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-8; Male; Pneumonia, Bacterial; Prognosis; Risk Assessment; Severity of Illness Index; Survival Analysis; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

Prestorage leukoreduction of red blood cell (RBC) bags prevents accumulation of pro-inflammatory mediators and experimentally attenuates post-transfusion inflammation in healthy dogs. However, the effect of leukoreduction on post-transfusion inflammation in critically ill dogs is unclear.. Dogs transfused with leukoreduced (LR) RBC will have lower concentrations of leukocytes, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (CRP) within 24 hours of post-transfusion compared to dogs transfused with nonleukoreduced (NLR) RBC.. Sixty-one RBC-transfused dogs (LR = 34, NLR = 27).. Randomized, blinded, controlled preliminary clinical trial. Blood bag processing was randomized to create identically appearing LR and NLR bags. Group allocation occurred with transfusion of the oldest compatible RBC bag. Blood samples were collected pretransfusion and at 8 and 24 hours post-transfusion for leukocyte count, IL-6, IL-8, MCP-1, and CRP. Data were analyzed on an intention-to-treat basis using linear mixed effects models. Significance was set at P < .05.. No significant differences were found between groups in concentrations of leukocytes (P = .93), IL-6 (P = .99), IL-8 (P = .75), MCP-1 (P = .69), or CRP (P = .18) over time. Eleven LR dogs (32%) and 4 NLR dogs (15%) were euthanized in the hospital (P = .14). No natural deaths occurred.. No differences in inflammation biomarker concentrations were detected over time between dogs transfused with LR or NLR RBC, but heterogeneity likely hampered the ability to detect a difference with this sample size. The novel randomization and enrollment protocol was successfully implemented across 2 participating institutions and will be easily scaled up for a future multicenter clinical trial.

Topics: Animals; Blood Preservation; Critical Illness; Dog Diseases; Dogs; Erythrocyte Transfusion; Inflammation; Interleukin-6; Interleukin-8

Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45;

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Biomarkers; Critical Illness; Follow-Up Studies; Humans; Inflammation; Interleukin-10; Interleukin-18; Interleukin-6; Interleukin-8; Interleukins; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Mortality; Recovery of Function; Renal Insufficiency, Chronic; Renal Replacement Therapy; Time Factors; Time-to-Treatment

Infections and infectious complications are the major cause of morbidity and mortality in febrile neutropenic patients after autologous stem cell transplantation. Laboratory biomarkers are helpful for early identification of critically ill patients and optimal therapy management. Several studies in adult non-neutropenic patients proposed sTREM-1 as a superior biomarker for identification of septic patients as well as a predictor for survival in these patients compared with procalcitonin (PCT), C-reactive protein (CRP), or interleukin-8 (IL-8). Here, to assess the utility of PCT, CRP, IL-8, and sTREM-1 in febrile neutropenia, 44 patients presenting with febrile neutropenia after autologous stem cell transplantation were recruited in a single-center prospective pilot study. We analyzed PCT and CRP as well as IL-8 and sTREM-1 levels pre- and post-transplantation at defined time points. In 20 of 44 patients, concentration of sTREM-1 was under the detection level at appearance of febrile neutropenia. Mean levels of PCT, IL-8, and CRP were significantly increased in infections of critically ill patients who by dysfunction or failure of one or more organs/system depend on survival from advanced instruments of monitoring and therapy. However, all tested biomarkers could not distinguish between presence and absence of bloodstream infection. The combination of the biomarkers PCT and IL-8 achieved a high sensitivity of 90% and specificity of 74% for the identification of serious complications in febrile neutropenia, whereas the combination of CRP and PCT or IL-8 achieved a high sensitivity of 100%, but with the addition of a low specificity of 47or 41%. In conclusion, we found that the measurement of sTREM-1 concentration at presentation of febrile neutropenia is not useful to identify bacterial bloodstream infections and critically ill patients. PCT and IL-8 are useful biomarkers for the early identification of critically ill patients, compared to CRP and sTREM-1 in febrile neutropenia. PCT or IL-8 in combination with clinical parameters should be considered in routine measurement to identify critically ill patients as early as possible.

Topics: Aged; Autografts; C-Reactive Protein; Calcitonin; Critical Illness; Febrile Neutropenia; Female; Humans; Interleukin-8; Male; Middle Aged; Stem Cell Transplantation; Triggering Receptor Expressed on Myeloid Cells-1

To determine whether regional anticoagulation of continuous renal replacement therapy circuits using citrate and calcium prolongs circuit life and/or affects circulating cytokine levels compared with regional anticoagulation using heparin and protamine.. Multicenter, parallel group randomized controlled trial.. Seven ICUs in Australia and New Zealand.. Critically ill adults requiring continuous renal replacement therapy.. Patients were randomized to receive one of two methods of regional circuit anticoagulation: citrate and calcium or heparin and protamine.. The primary outcome was functional circuit life measured in hours, assessed using repeated events survival analysis. In addition, we measured changes in interleukin-6, interleukin-8, and interleukin-10 blood levels. We randomized 212 subjects who were treated with 857 continuous renal replacement therapy circuits (median 2 circuits per patient [interquartile range, 1-6], 390 in citrate group vs 467 in heparin group). The groups were well matched for baseline characteristics. Patients receiving regional continuous renal replacement therapy anticoagulation with heparin and protamine were more likely to experience circuit clotting than those receiving citrate and calcium (hazard ratio, 2.03 [1.36-3.03]; p < 0.0005; 857 circuits). The median lifespan of the first study circuit in each patient was 39.2 hours (95% CI, 32.1-48.0 hr) in the citrate and calcium group versus 22.8 hours (95% CI, 13.3-34.0 hr) in the heparin and protamine group (log rank p = 0.0037, 204 circuits). Circuit anticoagulation with citrate and calcium had similar effects on cytokine levels compared with heparin and protamine anticoagulation. There were more adverse events in the group assigned to heparin and protamine anticoagulation (11 vs 2; p = 0.011).. Regional citrate and calcium anticoagulation prolongs continuous renal replacement therapy circuit life compared with regional heparin and protamine anticoagulation, does not affect cytokine levels, and is associated with fewer adverse events.

Topics: Aged; Aged, 80 and over; Anticoagulants; APACHE; Calcium; Citric Acid; Critical Illness; Female; Heparin; Humans; Intensive Care Units; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Protamines; Renal Replacement Therapy; Time Factors

Mechanical ventilation (MV) with high tidal volumes may induce or aggravate lung injury in critical ill patients. We compared the effects of a protective versus a conventional ventilatory strategy, on systemic and lung production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in patients without lung disease.. Patients without lung disease and submitted to mechanical ventilation admitted to one trauma and one general adult intensive care unit of two different university hospitals were enrolled in a prospective randomized-control study. Patients were randomized to receive MV either with tidal volume (VT) of 10 to 12 ml/kg predicted body weight (high VT group) (n = 10) or with VT of 5 to 7 ml/kg predicted body weight (low VT group) (n = 10) with an oxygen inspiratory fraction (FIO2) enough to keep arterial oxygen saturation >90% with positive end-expiratory pressure (PEEP) of 5 cmH2O during 12 hours after admission to the study. TNF-alpha and IL-8 concentrations were measured in the serum and in the bronchoalveolar lavage fluid (BALF) at admission and after 12 hours of study observation time.. Twenty patients were enrolled and analyzed. At admission or after 12 hours there were no differences in serum TNF-alpha and IL-8 between the two groups. While initial analysis did not reveal significant differences, standardization against urea of logarithmic transformed data revealed that TNF-alpha and IL-8 levels in bronchoalveolar lavage (BAL) fluid were stable in the low VT group but increased in the high VT group (P = 0.04 and P = 0.03). After 12 hours, BALF TNF-alpha (P = 0.03) and BALF IL-8 concentrations (P = 0.03) were higher in the high VT group than in the low VT group.. The use of lower tidal volumes may limit pulmonary inflammation in mechanically ventilated patients even without lung injury.. NCT00935896.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Critical Illness; Cytokines; Female; Humans; Inflammation; Intensive Care Units; Interleukin-8; Lung Diseases; Lung Injury; Male; Middle Aged; Pneumonia; Prospective Studies; Respiration, Artificial; Tidal Volume; Tumor Necrosis Factor-alpha

The effectiveness of plasma exchange (PE) with continuous hemodiafiltration (CHDF) in the treatment of critically ill patients was evaluated based on changes in cytokine levels. Twenty-six patients with acute hepatic failure were treated with PE (PE group) or PE and CHDF (PE+CHDF group), and the levels of cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were determined before and after treatment. Bilirubin levels were significantly lower after treatment in both the PE and PE+CHDF groups. There were no significant differences in TNF-alpha levels before and after treatment in the PE group, but the TNF-alpha level was significantly lower after treatment in the PE+CHDF group. There were no significant differences in the IL-6 levels before and after treatment in both the PE and PE+CHDF groups. There were no significant differences in IL-8 levels before and after treatment in the PE group, but the IL-8 level was significantly lower after treatment in the PE+CHDF group. PE with CHDF therapy was given to 5 patients with acutely aggravated autoimmune diseases, 2 patients with hemorrhagic shock and encephalopathy syndrome, and 3 patients with thrombotic microangiopathy. The results suggested that PE with CHDF therapy are useful in critically ill patients with suspected hypercytokinemia.

Topics: Adult; Aged; Autoimmune Diseases; Bilirubin; Blood Coagulation Disorders; Critical Illness; Cytokines; Female; Hemodiafiltration; Humans; Interleukin-6; Interleukin-8; Liver Failure, Acute; Male; Middle Aged; Plasma Exchange; Shock, Hemorrhagic; Tumor Necrosis Factor-alpha

Blood purification therapy is a method used to enable cytokine removal and to improve disturbed immune homeostasis in patients with sepsis or septic shock. This study aimed to evaluate the impact of HA 330 treatment on biochemical and hemodynamic parameters and cytokine levels in adult patients with septic shock.. Critically ill patients with septic shock who received continuous veno-venous hemodiafiltration and HA 330 treatment were included in this prospective observational study. Biochemical and hemodynamic parameters were followed throughout HA 330 treatment. Serum interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, high-mobility group box1 (HMGB-1) protein, IL-10 levels were analyzed by ELISA method, before and after each HA 330 session.. A total of 18 critically ill patients were included in this study. The median APACHE 2 score was 22.2 ± 7.49 and median SOFA score 9.6 ± 5.44 on intensive care unit admission. SOFA scores were significantly decreased on the 3rd day of HA 330 treatment, compared to 2nd day scores (p = 0.017). Median leukocyte value was significantly decreased (p = 0.027 and p = 0.024), while hemodynamic parameters remained unchanged throughout the HA 330 treatment. Median CRP and procalcitonin levels were significantly reduced at day 3 of HA 330 treatment compared to the baseline (p = 0.015 and p = 0.033, respectively). Serum IL-1 β, IL-6, IL-8, TNF-a, HMGB-1, and IL-10 levels decreased insignificantly by 11.5%, 26.4%, 11.4%, 37.9%, 0.02%, and 35.5%, respectively, at the end of the hemoperfusion treatment compared to the pre-treatment.. The administration of HA 330-based hemoperfusion in septic shock patients revealed improvements in SOFA scores, leukocyte count, and CRP and procalcitonin levels. However, there was no statistically significant change in concentrations of inflammatory cytokines and hemodynamic parameters during HA 330 treatment.

Topics: Adult; Continuous Renal Replacement Therapy; Critical Illness; Cytokines; HMGB Proteins; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Procalcitonin; Prognosis; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-10 and the antiviral cytokines IFN-α, IFN-β and IFN-λ1 were increased with disease severity. Remarkably, we found significantly lower levels of IFN-λ2,3 in critically ill patients compared to patients of the moderate and severe disease category. Finally, levels of IL-8, IL-6, IP-10, IL-10, IFN-α, IFN-β, IFN-γ and IFN-λ1 at baseline were positively associated with mortality, whereas higher IFN-λ2,3 levels were negatively associated with mortality.

Topics: Belgium; Chemokine CXCL10; Cohort Studies; COVID-19; Critical Illness; Cytokines; Humans; Immunoglobulin G; Interferon-alpha; Interleukin-10; Interleukin-6; Interleukin-8; Pandemics

The autonomic nervous system (ANS) can both modulate and be modulated by the inflammatory response during critical illness. We aimed to determine whether heart rate variability (HRV), a measure of ANS function, is associated with proinflammatory biomarker levels in critically ill children.. Two cohorts were analyzed. The first was a prospective observational cohort from August 2018 to August 2020 who had plasma proinflammatory cytokine measurements within 72 hours of admission, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-8. The second was a retrospective cohort from June 2012 to August 2020 who had at least one C-reactive protein (CRP) measurement within 72 hours of admission.. Forty-six-bed PICU.. Critically ill children in either cohort who had continuous heart rate data available from the bedside monitors.. None.. Sixty-two patients were included in the prospective cohort and 599 patients in the retrospective cohort. HRV was measured using the age-adjusted integer heart rate variability (HRVi), which is the sd of the heart rate sampled every 1 second over 5 consecutive minutes. The median HRVi was measured in the 12-hour period ending 30 minutes prior to inflammatory biomarker collection. HRVi was inversely correlated with IL-6, IL-8, and CRP levels (p ≤ 0.02); correlation with IL-8 and CRP persisted after adjusting for Pediatric Risk of Mortality III and age, and median HR and age (p < 0.001).. HRVi is inversely correlated with IL-6, IL-8, and CRP. Further studies are needed to validate this measure as a proxy for a proinflammatory state.

Topics: Biomarkers; Child; Critical Illness; Heart Rate; Humans; Interleukin-6; Interleukin-8; Prospective Studies; Retrospective Studies

Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity.. We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients' clinical characteristics.. We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients.. The Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10. LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.

Topics: Adult; Aged; B7-H1 Antigen; Bronchoalveolar Lavage Fluid; COVID-19; Critical Illness; Female; Humans; Interleukin-3 Receptor alpha Subunit; Interleukin-8; Male; Middle Aged; Neutrophils; Respiratory Distress Syndrome; SARS-CoV-2; Scavenger Receptors, Class E; Thrombosis

We hypothesised that plasma concentrations of biomarkers of neutrophil activation and pro-inflammatory cytokines differ according to the phase of rapidly evolving sepsis. In an observational study, we measured heparin-binding protein (HBP), myeloperoxidase (MPO), IL-6 and IL-8 in 167 sepsis patients on intensive care unit admission. We prospectively used the emergence of the first sepsis-associated organ dysfunction (OD) as a surrogate for the sepsis phase. Fifty-five patients (of 167, 33%) developed the first OD > 1 h before, 74 (44%) within ± 1 h, and 38 (23%) > 1 h after intensive care unit admission. HBP and MPO were elevated at a median of 12 h before the first OD, remained high up to 24 h, and were not associated with sepsis phase. IL-6 and IL-8 rose and declined rapidly close to OD emergence. Elevation of neutrophil activation markers HBP and MPO was an early event in the evolution of sepsis, lasting beyond the subsidence of the pro-inflammatory cytokine reaction. Thus, as sepsis biomarkers, HBP and MPO were not as prone as IL-6 and IL-8 to the effect of sample timing.

Topics: Aged; Antimicrobial Cationic Peptides; Biomarkers; Blood Proteins; Critical Illness; Female; Humans; Intensive Care Units; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutrophil Activation; Neutrophils; Peroxidase; Sepsis

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; COVID-19; Critical Illness; Female; Hospitalization; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Prognosis; Retrospective Studies; SARS-CoV-2; Young Adult

Inflammation has been believed to contribute to coronavirus disease 2019 (COVID-19). Risk factors for death of COVID-19 pneumonia have not yet been well established.In this retrospective cohort study, we included the deceased patients in COVID-19 specialized ICU with laboratory-confirmed COVID-19 from Guanggu hospital area of Tongji Hospital from February 8th to March 30th. Demographic, clinical, laboratory, and outcome data were extracted from electronic medical records using a standard data collection form. We used Spearman rank correlation and Cox regression analysis to explore the risk factors associated with in-hospital death, especially the association between inflammatory cytokines and death.A total of 205 severe/critical COVID-19 pneumonia patients were admitted in the COVID-19 specialized ICU and 75 deceased patients were included in the final analysis. The median age of the deceasing patients was 70 years (IQR 65-79). The common symptoms were fever (78.9%), cough (70.4%), and expectoration (39.4%). The BNP and CRP levels were far beyond the normal reference range. In the Spearman rank correlation analysis, IL-8 was found to be significantly associated with the time from onset to death (rs= -0.30, P = .034) and that from admission to death (rs= -0.32, P = .019). Cox regression showed after adjusting age and sex, IL-8 levels were still significantly associated with the time from onset to death (P = .003) and that from admission to death (P  = .01).IL-8 levels were associated with in-hospital death in severe/critical COVID-19 patients, which could help clinicians to identify patients with high risk of death at an early stage.

Topics: Adult; Aged; Aged, 80 and over; China; COVID-19; Critical Illness; Female; Hospital Mortality; Humans; Intensive Care Units; Interleukin-8; Male; Middle Aged; Pneumonia; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; SARS-CoV-2; Severity of Illness Index

In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Animals; Asymptomatic Infections; Betacoronavirus; China; Cohort Studies; Coronavirus Infections; COVID-19; Critical Illness; Disease Progression; Evolution, Molecular; Female; Genetic Variation; Genome, Viral; Hospitalization; Host-Pathogen Interactions; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Lymphocyte Count; Lymphopenia; Male; Middle Aged; Pandemics; Phylogeny; Pneumonia, Viral; Respiratory Distress Syndrome; SARS-CoV-2; T-Lymphocytes; Time Factors; Treatment Outcome; Virulence; Virus Shedding; Young Adult; Zoonoses

Topics: Acute-Phase Reaction; Adult; Aged; alpha 1-Antitrypsin; Betacoronavirus; Blotting, Western; Carrier Proteins; Case-Control Studies; Community-Acquired Infections; Coronavirus Infections; COVID-19; Critical Illness; Cytokines; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Hospitalization; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intensive Care Units; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Lactic Acid; Length of Stay; Male; Membrane Proteins; Middle Aged; Neutrophils; Pandemics; Phosphorylation; Pneumonia; Pneumonia, Viral; Receptors, Tumor Necrosis Factor, Type I; SARS-CoV-2; Severity of Illness Index; Thyroid Hormone-Binding Proteins; Thyroid Hormones

Topics: Aged; APACHE; Cardiovascular Diseases; Cohort Studies; Critical Illness; Disseminated Intravascular Coagulation; Extracellular Traps; Female; Gastrointestinal Diseases; Humans; Intensive Care Units; Interleukin-8; Kidney Diseases; Male; Middle Aged; Mitogen-Activated Protein Kinases; Mortality; Multivariate Analysis; Nervous System Diseases; Neutrophils; Organ Dysfunction Scores; Prospective Studies; Reproducibility of Results; Respiratory Tract Diseases; Risk Assessment; Sepsis; Wounds and Injuries

To determine whether biomarkers of endothelial activation and inflammation provide added value for prediction of in-hospital mortality within 28 days when combined with physician judgment in critically ill emergency department patients.. Prospective, observational study.. Two urban, academic emergency departments, with ≈80,000 combined annual visits, between June 2016 and December 2017.. Admitted patients, greater than 17 years old, with two systemic inflammatory response syndrome criteria and organ dysfunction, systolic blood pressure less than 90 mm Hg, or lactate greater than 4.0 mmol/L. Patients with trauma, intracranial hemorrhage known prior to arrival, or without available blood samples were excluded.. Emergency department physicians reported likelihood of in-hospital mortality (0-100%) by survey at hospital admission. Remnant EDTA blood samples, drawn during the emergency department stay, were used to measure angiopoietin-1, angiopoietin-2, tumor necrosis factor receptor-1, interleukin-6, and interleukin-8.. We screened 421 patients and enrolled 314. The primary outcome of in-hospital mortality within 28 days occurred in 31 (9.9%). When predicting the primary outcome, the best biomarker model included angiopoietin-2 and interleukin-6 and performed moderately well (area under the curve, 0.72; 95% CI, 0.69-0.75), as did physician judgment (area under the curve, 0.78; 95% CI, 0.74-0.82). Combining physician judgment and biomarker models improved performance (area under the curve, 0.85; 95% CI, 0.82-0.87), with area under the curve change of 0.06 (95% CI, 0.04-0.09; p < 0.01) compared with physician judgment alone.. Predicting in-hospital mortality within 28 days among critically ill emergency department patients may be improved by including biomarkers of endothelial activation and inflammation in combination with emergency department physician judgment.

Topics: Angiopoietin-1; Angiopoietin-2; Biomarkers; Clinical Decision-Making; Critical Illness; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Intensive Care Units; Interleukin-6; Interleukin-8; Intubation; Judgment; Length of Stay; Male; Medical Staff, Hospital; Middle Aged; Prospective Studies; Receptors, Tumor Necrosis Factor, Type I; Sampling Studies; Vasoconstrictor Agents; Washington

Acute-on-chronic liver failure (ACLF) develops in acute decompensation (AD) of cirrhosis and shows high mortality. In critically ill patients, early diagnosis of ACLF could be important for therapeutic decisions (eg, renal replacement, artificial liver support, liver transplantation). This study evaluated fibroblast growth factor 21 (FGF21) as a marker of mitochondrial dysfunction in the context of ACLF. The study included 154 individuals (112 critically patients and 42 healthy controls) divided into a training and a validation cohort. In the training cohort of 42 healthy controls and 34 critically ill patients (of whom 24 were patients with cirrhosis), levels of FGF21, interleukin (IL) 6, and IL8 were measured. In the validation cohort of 78 patients with cirrhosis, 17 patients were admitted with or developed ACLF during follow-up and underwent daily clinical and nutritional assessment. Levels of FGF21 were higher in critically ill patients, especially in patients with cirrhosis admitted to the intensive care unit (ICU). Moreover, FGF21 as well as IL6 and IL8 levels were higher in patients with ACLF, but they did not increase with the severity of ACLF. Interestingly, in the validation cohort, FGF21 was also elevated in the patients who developed ACLF in the next 7 days. In these patients, FGF21 levels were an independent predictor of ACLF presence and development in multivariate analysis together with Child-Pugh score. FGF21 levels had no impact on the survival of critically ill patients with cirrhosis. In conclusion, this study demonstrates that FGF21 levels are of specific diagnostic value regarding the presence and development of ACLF in patients admitted to ICU for AD of liver cirrhosis. Further studies are warranted to address pathophysiological and possible therapeutic implications. Liver Transplantation 24 595-605 2018 AASLD.

Topics: Acute-On-Chronic Liver Failure; Adolescent; Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Case-Control Studies; Chi-Square Distribution; Critical Illness; Female; Fibroblast Growth Factors; Germany; Humans; Interleukin-6; Interleukin-8; Kaplan-Meier Estimate; Liver Cirrhosis; Logistic Models; Male; Mexico; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Reproducibility of Results; Risk Factors; ROC Curve; Time Factors; Up-Regulation; Young Adult

To investigate whether patients who develop ICU-acquired weakness have a different pattern of systemic inflammatory markers compared with critically ill patients who do not develop ICU-acquired weakness.. Prospective observational cohort study.. Mixed medical-surgical ICU of a tertiary care hospital in the Netherlands.. Newly admitted critically ill patients, greater than or equal to 48 hours on mechanical ventilation with a nonneurologic ICU admission diagnosis, were included.. A panel of systemic inflammatory markers and soluble vascular adhesion molecules were measured in plasma samples of day 0, 2, and 4 after ICU admission. ICU-acquired weakness was diagnosed by manual muscle strength testing as soon as patients were awake and attentive.. Ninety-nine of 204 included patients developed ICU-acquired weakness. Principal component regression analysis, adjusted for confounders, showed that principal component 1, mainly loaded with interleukin-6, interleukin-8, interleukin-10, and fractalkine, was significantly higher in patients who developed ICU-acquired weakness (odds ratio, 1.35 [95% CI, 1.18-1.55]). Partial least squares-discriminant analysis also showed that these markers were the most important discriminative markers. Mixed-effects models of these markers showed that ICU-acquired weakness was associated with an independent 1.5- to two-fold increase in these markers.. Systemic inflammation is increased in patients who develop ICU-acquired weakness compared with patients who do not develop ICU-acquired weakness in the first 4 days after ICU admission. This finding is consistent when adjusted for confounders, like disease severity. A group consisting of interleukin-6, interleukin-8, interleukin-10, and fractalkine was identified to be the most important.

Topics: Aged; Biomarkers; Chemokine CX3CL1; Critical Illness; Female; Humans; Inflammation; Inflammation Mediators; Intensive Care Units; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Muscle Strength; Muscle Weakness; Netherlands; Prospective Studies; Regression Analysis; Respiration, Artificial; Systemic Inflammatory Response Syndrome; Tertiary Care Centers; Time Factors

Experimental studies suggest that calcium channel blockers can improve sepsis outcome. The aim of this study was to determine the association between prior use of calcium channel blockers and the outcome of patients admitted to the ICU with sepsis.. A prospective observational study.. The ICUs of two tertiary care hospitals in the Netherlands.. In total, 1,060 consecutive patients admitted with sepsis were analyzed, 18.6% of whom used calcium channel blockers.. None.. Considering large baseline differences between calcium channel blocker users and nonusers, a propensity score matched cohort was constructed to account for differential likelihoods of receiving calcium channel blockers. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured during the first 4 days after admission. Severity of illness over the first 24 hours, sites of infection and causative pathogens were similar in both groups. Prior use of calcium channel blockers was associated with improved 30-day survival in the propensity-matched cohort (20.2% vs 32.9% in non-calcium channel blockers users; p = 0.009) and in multivariate analysis (odds ratio, 0.48; 95% CI, 0.31-0.74; p = 0.0007). Prior calcium channel blocker use was not associated with changes in the plasma levels of host biomarkers indicative of activation of the cytokine network, the vascular endothelium and the coagulation system, with the exception of antithrombin levels, which were less decreased in calcium channel blocker users.. Prior calcium channel blocker use is associated with reduced mortality in patients following ICU admission with sepsis.

Topics: Aged; Antithrombins; APACHE; Biomarkers; Calcium Channel Blockers; Critical Illness; Female; Humans; Intensive Care Units; Interleukin-6; Interleukin-8; Male; Middle Aged; Propensity Score; Prospective Studies; Protein C; Sepsis

The purpose of the study is to evaluate the incidence, association with serum cytokine profile, and prognostic value of thrombocytopenia, in critically ill patients with severe sepsis/septic shock.. A cohort of 105 consecutive patients admitted in intensive care unit was included in our analysis. Serum levels of intercellular adhesion molecule, vascular cell adhesion molecule, interferon γ, interleukin 8, and soluble form of the urokinase-type plasminogen activator receptor (suPAR) were measured.. Thrombocytopenia was observed in 53% of patients at the time of admission. Platelet counts showed a statistically significant negative correlation with serum levels of intercellular adhesion molecule, suPAR, and interleukin 8 (P < .0001). In multivariate analysis, high Acute Physiological and Chronic Health Evaluation II score, high serum suPAR, and low platelet counts were associated with increased mortality, and receiver operating characteristic curve analysis was used to determine the best cutoff value for mortality prediction. Each variable with a value above or below the predefined cutoff levels were given 1 point. Patients were categorized in risk groups based on total point score. High-risk (2-3), intermediate-risk (1), and low-risk (0 points) groups consisted of 43%, 22%, and 35% and 28-day mortality was observed in 69%, 26%, and 3% of the patients in each group, respectively.. Thrombocytopenia is associated with poor prognosis and a distinct serum cytokine profile.

Topics: Adult; Aged; Biomarkers; Critical Care; Critical Illness; Cytokines; Female; Greece; Hospital Mortality; Humans; Incidence; Interleukin-8; Male; Middle Aged; Prognosis; Prospective Studies; Receptors, Urokinase Plasminogen Activator; ROC Curve; Sepsis; Thrombocytopenia

Immunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; however, it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics.. We conducted a prospective cohort study of patients admitted to the medical intensive care unit of an academic medical center with severe sepsis. Patients were followed for the development of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality. Plasma proteins, representing the host inflammatory response, anti-inflammatory response, and endothelial leak were measured in 30 % of subjects. Clinical characteristics and plasma protein concentrations of patients with neutropenia at enrollment were compared to patients without neutropenia.. Of 797 subjects enrolled, 103 (13 %) were neutropenic at ICU admission. The neutropenic subjects were more often in shock, admitted from the hospital ward, had higher APACHE III scores, and more likely bacteremic. Neutropenia was an independent risk factor for AKI (RR 1.28; 95 % CI 1.04, 1.57; p = 0.03), but not ARDS (RR 0.90; 95 % CI 0.70, 1.17; p = 0.42) or 30-day mortality (RR 1.05; 95 % CI 0.85, 1.31; p = 0.65). Neutropenic subjects had higher plasma interleukin (IL)-6 (457 vs. 249 pg/ml; p = 0.03), IL-8 (581 vs. 94 pg/ml; p <0.001), and granulocyte colony-stimulating factor (G-CSF) (3624 vs. 99 pg/ml; p <0.001). Angiopoietin-2 and IL-1 receptor antagonist concentrations did not differ between groups.. Neutropenic sepsis is associated with a higher AKI risk and concentrations of inflammatory mediators IL-6, IL-8, and G-CSF relative to non-neutropenic patients. These differences may have implications for future therapies targeting neutropenic sepsis.

Topics: Acute Kidney Injury; Adult; Aged; Angiopoietin-2; APACHE; Biomarkers; Chi-Square Distribution; Cohort Studies; Critical Illness; Female; Granulocyte Colony-Stimulating Factor; Humans; Intensive Care Units; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Neutropenia; Pennsylvania; Prospective Studies; Receptors, Interleukin-1; Respiratory Distress Syndrome; Sepsis

Diabetes is associated with chronic inflammation and activation of the vascular endothelium and the coagulation system, which in a more acute manner are also observed in sepsis. Insulin and metformin exert immune modulatory effects. In this study, we aimed to determine the association of diabetes and preadmission insulin and metformin use with sepsis outcome and host response.. We evaluated 1104 patients with sepsis, admitted to the intensive care unit and stratified according to the presence or absence of diabetes mellitus. The host response was examined by a targeted approach (by measuring 15 plasma biomarkers reflective of pathways implicated in sepsis pathogenesis) and an unbiased approach (by analyzing whole genome expression profiles in blood leukocytes).. Diabetes mellitus was not associated with differences in sepsis presentation or mortality up to 90 days after admission. Plasma biomarker measurements revealed signs of systemic inflammation, and strong endothelial and coagulation activation in patients with sepsis, none of which were altered in those with diabetes. Patients with and without diabetes mellitus, who had sepsis demonstrated similar transcriptional alterations, comprising 74 % of the expressed gene content and involving over-expression of genes associated with pro-inflammatory, anti-inflammatory, Toll-like receptor and metabolic signaling pathways and under-expression of genes associated with T cell signaling pathways. Amongst patients with diabetes mellitus and sepsis, preadmission treatment with insulin or metformin was not associated with an altered sepsis outcome or host response.. Neither diabetes mellitus nor preadmission insulin or metformin use are associated with altered disease presentation, outcome or host response in patients with sepsis requiring intensive care.

Topics: Aged; Biomarkers; Chemokine CX3CL1; Critical Illness; Diabetes Mellitus; E-Selectin; Female; Humans; Hyperglycemia; Inflammation; Insulin; Intensive Care Units; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Metformin; Middle Aged; Prospective Studies; Sepsis; Statistics, Nonparametric; Survival Analysis; Treatment Outcome; Tumor Necrosis Factor-alpha

Higher plasma concentrations of inflammatory and apoptosis markers in critically ill patients receiving RRT are associated with RRT dependence and death. This study objective was to examine whether plasma inflammatory (IL-6, -8, -10, and -18; macrophage migration inhibitory factor) and apoptosis (death receptor-5, tumor necrosis factor receptor I and II) biomarkers augment risk prediction of renal recovery and mortality compared with clinical models.. The Biologic Markers of Recovery for the Kidney study (n=817) was a prospective, nested, observational cohort study conducted as an ancillary to the Veterans Affairs/National Institutes of Health Acute renal failure Trial Network study, a randomized trial of intensive versus less intensive RRT in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 Veterans Affairs- and university-affiliated centers. Primary outcomes of interest were renal recovery and mortality at day 60.. A parsimonious clinical model consisting of only four variables (age, mean arterial pressure, mechanical ventilation, and bilirubin) predicted renal recovery (area under the receiver-operating characteristic curve [AUROC], 0.73; 95% confidence interval [95% CI], 0.68 to 0.78) and mortality (AUROC, 0.74; 95% CI, 0.69 to 0.78). By contrast, individual biomarkers were only modestly predictive of renal recovery (AUROC range, 0.55-0.63) and mortality (AUROC range, 0.54-0.68). Adding plasma IL-8 to a parsimonious model augmented prediction of recovery (AUROC, 0.76; 95% CI, 0.71 to 0.81; P=0.04) and mortality (AUROC, 0.78; 95% CI, 0.73 to 0.82; P<0.01) compared with the clinical model alone.. This study suggests that a simple four-variable clinical model with plasma IL-8 had predictive value for renal recovery and mortality. These findings require external validation but could easily be used by clinicians.

Topics: Age Factors; Apoptosis Regulatory Proteins; Area Under Curve; Arterial Pressure; Bilirubin; Biomarkers; Critical Illness; Humans; Inflammation Mediators; Interleukin-8; Kidney; Kidney Diseases; Models, Biological; Predictive Value of Tests; Prospective Studies; Recovery of Function; Renal Replacement Therapy; Respiration, Artificial; Risk Assessment; Risk Factors; ROC Curve; Time Factors; Treatment Outcome; United States; United States Department of Veterans Affairs

Enteral supply of ω-3 polyunsaturated fatty acids has been used in an attempt to modulate inflammation and improve outcome in critically ill patients. However, enteral administration may be slow to change membrane composition and therefore may not be the best route to supply these fatty acids in patients with acute conditions. This study evaluated the effects of short-term intravenous (IV) administration of fish oil-based lipid emulsion (FLE) as pharmaconutrition on cytokine levels in critically ill elderly patients.. Enterally fed patients (n = 40; aged 60-80 years) were recruited in the first 48 hours of intensive care unit (ICU) admission. Fifteen patients received IV FLE (0.2 g/kg body weight) over 6 hours for 3 consecutive days, and 25 patients did not receive IV lipid (control). Samples were collected before and 24 hours and 72 hours after the third FLE infusion. Nutrient intakes, clinical parameters, and serum cytokine concentrations were measured.. Compared with the control, FLE resulted in higher energy intake, lower serum tumor necrosis factor-α and interleukin (IL)-8 concentrations, and higher serum IL-10. These differences occurred around 7-9 days of ICU stay at the time of the patient's extubation. ICU stay, mortality, and markers of coagulation and liver function did not differ between groups.. Short-term IV FLE modulates some inflammatory markers in critically ill elderly patients receiving enteral nutrition (EN), suggesting an anti-inflammatory effect. This may be a benefit and suggests a role for FLE administration as a supplement in elderly ICU patients receiving standard EN.

Topics: Aged; Critical Illness; Cytokines; Emulsions; Energy Intake; Enteral Nutrition; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Inflammation Mediators; Intensive Care Units; Interleukin-10; Interleukin-8; Length of Stay; Male; Tumor Necrosis Factor-alpha

Current clinical prediction scores for acute lung injury (ALI) have limited positive predictive value. No studies have evaluated predictive plasma biomarkers in a broad population of critically ill patients or as an adjunct to clinical prediction scores.. To determine whether plasma angiopoietin-2 (Ang-2), von Willebrand factor (vWF), interleukin-8 (IL-8), and/or receptor for advanced glycation end products (sRAGE) predict ALI in critically ill patients.. Plasma samples were drawn from critically ill patients (n = 230) identified in the emergency department. Patients who had ALI at baseline or in the subsequent 6 hours were excluded, and the remaining patients were followed for development of ALI.. Nineteen patients developed ALI at least 6 hours after the sample draw. Higher levels of Ang-2 and IL-8 were significantly associated with increased development of ALI (P = 0.0008, 0.004, respectively). The association between Ang-2 and subsequent development of ALI was robust to adjustment for sepsis and vasopressor use. Ang-2 and the Lung Injury Prediction Score each independently discriminated well between those who developed ALI and those who did not (area under the receiver operating characteristic curve, 0.74 for each), and using the two together improved the area under the curve to 0.84 (vs. 0.74, P = 0.05). In contrast, plasma levels of sRAGE and vWF were not predictive of ALI.. Plasma biomarkers such as Ang-2 can improve clinical prediction scores and identify patients at high risk for ALI. In addition, the early rise of Ang-2 emphasizes the importance of endothelial injury in the early pathogenesis of ALI.

Topics: Acute Lung Injury; Aged; Aged, 80 and over; Angiopoietin-2; Biomarkers; Critical Illness; Decision Support Techniques; Female; Humans; Interleukin-8; Male; Middle Aged; Prospective Studies; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Regression Analysis; Risk Factors; ROC Curve; Sensitivity and Specificity; von Willebrand Factor

The aim of the present study was to describe the variation in adiponectin and resistin levels, 2 adipokines with opposing effects on metabolism, in mechanically ventilated patients with sepsis and their relationships to disease severity and cytokine levels.. An observational prospective study was conducted in a secondary/tertiary unit. Forty-one mechanically ventilated patients diagnosed as having sepsis were included in the study. The Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were estimated. Adiponectin, resistin, and cytokines were measured upon sepsis diagnosis and every 3 to 4 days thereafter until day 30. Adiponectin and resistin were also measured in 40 controls.. The patients had higher adiponectin (10.9 ± 6.1 μg/mL vs 6.0 ± 2.9 μg/mL, P < .001) and resistin (24.7 ng/mL vs 3.8 ng/mL, P < .001) levels compared with the controls. Adiponectin increased and resistin decreased significantly over time in the entire cohort. Resistin correlated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, interleukin (IL)-6, IL-8, and IL-10 and was significantly higher in severe sepsis/septic shock compared with sepsis. No correlations between adiponectin and clinical scores were noted.. Adiponectin and resistin change reciprocally during the course of sepsis. Resistin relates to the severity of sepsis and the degree of inflammatory response. Adiponectin and resistin may play a critical role in the metabolic adaptations observed in sepsis.

Topics: Adiponectin; Adult; APACHE; Critical Illness; Cytokines; Female; Health Status Indicators; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Organ Dysfunction Scores; Prospective Studies; Resistin; Sepsis; Time Factors

Interleukin-8 (IL-8) is a central chemokine in acute respiratory distress syndrome (ARDS), and the IL-8 gene contains a functional single nucleotide polymorphism (SNP) -251A/T in its promoter region. We hypothesized that IL-8 -251A/T SNP is associated with PaO(2)/FiO(2) in critically ill patients.. We conducted genetic-association studies in intensive care units at academic teaching centres using a derivation septic shock cohort (vasopressin and septic shock trial (VASST), n = 467) and a validation post-cardiopulmonary bypass surgery cohort (CPB, n = 739) of Caucasian patients. Patients in both cohorts were genotyped for IL-8 -251A/T. The primary outcome variable in both cohorts was the fraction of patients who had a PaO(2) /FiO(2) < 200. IL-8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro.. The frequency of the patients with PaO(2)/FiO(2) <200 was significantly greater in patients who had the AA genotype of -251A/T than in patients who had the AT or TT genotypes in both VASST (AA = 60.8% vs AT and TT = 53.8% and 48.0%, P = 0.038) and the CPB cohort (AA = 37.0% vs AT and TT = 27.0% and 26.0%, P = 0.039). Patients having the AA genotype had a higher probability to remain on mechanical ventilation (P = 0.047) in the first 14 days. Lymphoblastoid cells having the AA genotype had significantly higher IL-8 mRNA expression than cells having the AT or TT genotype (P = 0.022).. Critically ill Caucasian patients who had the AA genotype of IL-8 -251A/T had an increased risk of PaO(2)/FiO(2) <200. The AA genotype was associated with greater IL-8 mRNA expression than the AT or TT genotypes.

Topics: Aged; Cardiopulmonary Bypass; Cells, Cultured; Cohort Studies; Critical Illness; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Intensive Care Units; Interleukin-8; Male; Middle Aged; Oxygen; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Respiration, Artificial; Respiratory Distress Syndrome; Severity of Illness Index; Shock, Septic

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Critical Care; Critical Illness; Early Diagnosis; Female; Fever; Humans; Intensive Care Units; Interleukin-8; Male; Membrane Glycoproteins; Neutropenia; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Survival Analysis; Triggering Receptor Expressed on Myeloid Cells-1

Delirium occurs frequently in critically ill patients and is associated with disease severity and infection. Although several pathways for delirium have been described, biomarkers associated with delirium in intensive care unit (ICU) patients is not well studied. We examined plasma biomarkers in delirious and nondelirious patients and the role of these biomarkers on long-term cognitive function.. In an exploratory observational study, we included 100 ICU patients with or without delirium and with ("inflamed") and without ("noninflamed") infection/systemic inflammatory response syndrome (SIRS). Delirium was diagnosed by using the confusion-assessment method-ICU (CAM-ICU). Within 24 hours after the onset of delirium, blood was obtained for biomarker analysis. No differences in patient characteristics were found between delirious and nondelirious patients. To determine associations between biomarkers and delirium, univariate and multivariate logistic regression analyses were performed. Eighteen months after ICU discharge, a cognitive-failure questionnaire was distributed to the ICU survivors.. In total, 50 delirious and 50 nondelirious patients were included. We found that IL-8, MCP-1, procalcitonin (PCT), cortisol, and S100-β were significantly associated with delirium in inflamed patients (n = 46). In the noninflamed group of patients (n = 54), IL-8, IL-1ra, IL-10 ratio Aβ1-42/40, and ratio AβN-42/40 were significantly associated with delirium. In multivariate regression analysis, IL-8 was independently associated (odds ratio, 9.0; 95% confidence interval (CI), 1.8 to 44.0) with delirium in inflamed patients and IL-10 (OR 2.6; 95% CI 1.1 to 5.9), and Aβ1-42/40 (OR, 0.03; 95% CI, 0.002 to 0.50) with delirium in noninflamed patients. Furthermore, levels of several amyloid-β forms, but not human Tau or S100-β, were significantly correlated with self-reported cognitive impairment 18 months after ICU discharge, whereas inflammatory markers were not correlated to impaired long-term cognitive function.. In inflamed patients, the proinflammatory cytokine IL-8 was associated with delirium, whereas in noninflamed patients, antiinflammatory cytokine IL-10 and Aβ1-42/40 were associated with delirium. This suggests that the underlying mechanism governing the development of delirium in inflamed patients differs from that in noninflamed patients. Finally, elevated levels of amyloid-β correlated with long-term subjective cognitive-impairment delirium may represent the first sign of a (subclinical) dementia process. Future studies must confirm these results.The study was registered in the Clinical Trial Register (NCT00604773).

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Chemokine CCL2; Chi-Square Distribution; Cognition Disorders; Critical Illness; Delirium; Female; Humans; Hydrocortisone; Inflammation; Interleukin-8; Interleukins; Logistic Models; Male; Middle Aged; Nerve Growth Factors; Protein Precursors; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Statistics, Nonparametric

Inflammatory markers have been assessed for the diagnosis and follow-up of ventilator-associated pneumonia (VAP), but their potential role in predicting the risk for VAP is unknown. We prospectively assessed the evolution of cytokines in mechanically ventilated patients and their predictive and diagnostic role for VAP.. Prospective observational study.. Medical intensive care unit.. Mechanically ventilated patients. Exclusion criteria were active infection at admission and subsequent extrapulmonary infection.. None.. Sequential measurements of interleukin (IL)-1, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha were done in 44 ventilated patients. VAP was suspected in 20 cases and microbiologically confirmed in nine. At admission, demographics, severity scores, and clinical and standard laboratory values did not discriminate patients with and without VAP, but the median (interquartile range) serum levels of IL-6 were higher in patients who subsequently developed VAP, compared with those without VAP (235 [141-803] vs. 113 [60-170] pg/mL, p = 0.015). The sensitivity and specificity of IL-6 to predict VAP was 71% and 78%, respectively, using 198 pg/mL as optimal cutoff, with relative risk (95% confidence interval) 8.9 (1.4-56.3). When VAP was suspected, serum levels of IL-6 were higher in patients with confirmed compared with nonconfirmed VAP (1131 [496-1987] vs. 236 [115-357] pg/mL, p = 0.016). The sensitivity and specificity to discriminate between confirmed and nonconfirmed VAP was 71% and 89%, respectively, using 620 pg/mL as optimal cutoff, with relative risk (95% confidence interval) 15.0 (1.2-185.2).. IL-6 at admission is an early and accurate indicator of patients at increased risk for VAP. IL-6 is also accurate in discriminating patients with VAP from other causes of pulmonary infiltrates. Extrapolation of these results to the overall population of critically ill patients is limited by the small number of patients.

Topics: Aged; Cohort Studies; Critical Care; Critical Illness; Female; Hospital Mortality; Humans; Inflammation Mediators; Intensive Care Units; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Pneumonia, Ventilator-Associated; Predictive Value of Tests; Probability; Prognosis; Prospective Studies; Respiration, Artificial; Respiratory Insufficiency; Risk Assessment; Sensitivity and Specificity; Statistics, Nonparametric; Survival Analysis; Systemic Inflammatory Response Syndrome

Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF.. The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness.. When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients.. There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.

Topics: Acute Kidney Injury; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cohort Studies; Critical Illness; Cytokines; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Renal Dialysis; Systemic Inflammatory Response Syndrome

Topics: APACHE; Biomarkers; Critical Illness; Cytokines; Female; Humans; Intensive Care Units; Interleukin-8; Male; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis; Tumor Necrosis Factor-alpha

The aim of the present study was to determine whether the presence of an infectious focus or of fever alone can predict bloodstream infection and whether levels of C-reactive protein, procalcitonin, interleukin (IL)-6, IL-8, and soluble IL-2 receptor (sIL-2R) improve the diagnosis of community-acquired bloodstream infection. Markers of systemic inflammation were studied in 92 patients with community-acquired infection. On admission to hospital, 54 patients had an infectious focus, 25 had fever without an infectious focus, and 13 had neither. The presence of focus or fever predicted bloodstream infection (n=13 patients) with a sensitivity of 100% (95% confidence interval, 75-100), a specificity of 16% (95%CI, 9-26), a negative predictive value of 100% (95%CI, 75-100), and a positive predictive value of 16% (95%CI, 9-26). Positive predictive values of C-reactive protein, procalcitonin, IL-6, IL-8, and sIL-2R, all measured on admission, were also low (33-44%). Eight febrile patients in whom an infectious focus was found during a 3-day follow-up period had higher on-admission IL-6 (P=0.005) and sIL-2R (P=0.046) levels than did 17 febrile patients without an infectious focus. In conclusion, markers of systemic inflammation do not improve the diagnosis of community-acquired bloodstream infection; however, they may aid in identifying patients with fever due to occult infection.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Biomarkers; Blood-Borne Pathogens; C-Reactive Protein; Cohort Studies; Confidence Intervals; Critical Illness; Emergency Service, Hospital; Female; Finland; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Prognosis; Receptors, Interleukin-2; Risk Assessment; ROC Curve; Sampling Studies; Sensitivity and Specificity; Shock, Septic; Survival Rate

Ubiquitin is suggested to play a key role in essential intracellular functions, such as heat shock response, protein breakdown, and regulation of immune responses. Ubiquitin has also been detected in the extracellular space, but the function and biologic significance is unclear. We describe a new function of extracellular ubiquitin and show that extracellular ubiquitin specifically inhibits ex vivo secretion of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha mRNA expression from peripheral blood mononuclear cells (PBMNCs) in response to endotoxin in a dose-dependent manner. In contrast, the TNF-alpha response to zymosan or Staphylococcus aureus as well as the interleukin-6 (IL-6) and IL-8 responses to endotoxin were unaffected by ubiquitin. Measurement of serum ubiquitin levels showed a significant 5- to 7-fold increase in sepsis and trauma patients, to the level required for inhibition of the PBMNC TNF-alpha response to endotoxin by ubiquitin. Elevated ubiquitin levels in serum were significantly correlated with a reduced TNF-alpha production. Antibodies to ubiquitin were able to (1) significantly increase (2- to 5-fold) the TNF-alpha response to endotoxin in whole blood from trauma and sepsis patients, (2) completely neutralize the inhibitory effect of trauma patients' serum on healthy donors' TNF-alpha production, and (3) partially neutralize the inhibitory effect of sepsis patients' serum on healthy donors' TNF-alpha production. Ubiquitin-depleted serum from trauma patients lost the inhibitory activity for TNF-alpha production, whereas extracted endogenous ubiquitin exerts the inhibitory activity. The results demonstrate that extracellular ubiquitin acts as a cytokinelike protein with anti-inflammatory properties and indicate that extracellular ubiquitin is involved in the regulation of immunodepression in critical illness.

Topics: Adult; Animals; Cattle; Cells, Cultured; Critical Illness; Depression, Chemical; Endotoxins; Female; Gene Expression Regulation; Humans; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Multiple Trauma; RNA, Messenger; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha; Ubiquitin; Wounds, Nonpenetrating

To elucidate the diagnostic accuracy of granulocyte colony-stimulating factor (G-CSF), interleukin-8 (IL-8), and interleukin-1 receptor antagonist (IL-1ra) in identifying patients with sepsis among critically ill pediatric patients with suspected infection.. Nested case-control study in a multidisciplinary neonatal and pediatric intensive care unit (PICU) PATIENTS: PICU patients during a 12-month period with suspected infection, and plasma available from the time of clinical suspicion (254 episodes, 190 patients).. Plasma levels of G-CSF, IL-8, and IL-1ra. Episodes classified on the basis of clinical and bacteriological findings into: culture-confirmed sepsis, probable sepsis, localized infection, viral infection, and no infection. Plasma levels were significantly higher in episodes of culture-confirmed sepsis than in episodes with ruled-out infection. The area under the receiver operating characteristic curve was higher for IL-8 and G-CSF than for IL-1ra. Combining IL-8 and G-CSF improved the diagnostic performance, particularly as to the detection of Gram-negative sepsis. Sensitivity was low (<50%) in detecting Staphylococcus epidermidis bacteremia or localized infections.. In this heterogeneous population of critically ill children with suspected infection, a model combining plasma levels of IL-8 and G-CSF identified patients with sepsis. Negative results do not rule out S. epidermidis bacteremia or locally confined infectious processes. The model requires validation in an independent data-set.

Topics: Area Under Curve; Case-Control Studies; Child; Child, Preschool; Critical Illness; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infant; Infections; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Logistic Models; Male; Sensitivity and Specificity; Sialoglycoproteins

To determine nuclear factor kappa B (NF-kappa B) activation in mononuclear and neutrophils from critically ill patients and to compare NF-kappa B activation with circulating concentrations of interleukin (IL)-6, IL-8, and soluble intercellular adhesion molecule (sICAM)-1.. Observational study.. University Teaching Hospital, eight-bed intensive care unit in northeast Scotland.. Ten patients admitted to the intensive care unit who fulfilled the criteria for systemic inflammatory response syndrome were studied at 0, 24, 48, and 72 hrs. Six healthy volunteers were also studied.. None.. NF-kappa B activation was significantly higher in patients compared to healthy volunteers in both neutrophils (p = .001) and mononuclear leukocytes (p = .013). In the six patients who survived to 96 hrs, the level of NF-kappa B activation in mononuclear cells remained constant (p = .9). However, in the four patients who died before 96 hrs, mononuclear cell NF-kappa B activation increased markedly and was significantly higher before death than in those who survived to 96 hrs (p = .0105). NF-kappa B activation in neutrophils similarly remained constant in patients who survived to 96 hrs (p = .4) but did not show the same increase before death. Circulating concentrations of IL-6, IL-8, and sICAM-1 were elevated but were unrelated to leukocyte NF-kappa B activation.. We found NF-kappa B activation in mononuclear and neutrophils in patients with systemic inflammatory response syndrome, which increased markedly before death in mononuclear leukocytes and was not related to plasma IL-6, IL-8, and sICAM-1 concentrations. These data support the need for further study of the role of NF-kappa B activation in mortality from systemic inflammatory response syndrome and sepsis.

Topics: Adult; Aged; Analysis of Variance; APACHE; Critical Illness; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Neutrophils; NF-kappa B; Solubility; Statistics, Nonparametric; Time Factors

We studied the value of serum interleukin-8 (IL-8) and procalcitonin (PCT) in the early diagnosis of early severe bacterial infection in 58 critically ill ventilated neonates. ELISA was used for determining IL-8 and immunoluminometric assay for PCT. IL-8 and PCT were compared with routinely used serum C-reactive protein (CRP). Neonates were divided into four groups: Ia--proven severe bacterial infection (n = 9), Ib--clinical sepsis (n = 16), II--respiratory distress without bacterial infection (n = 12), and III--various types of neonatal distress (n = 21). Sera were collected on admission, at 24 h and 48 h after admission. There was no significant difference between groups Ia and Ib for either parameter at any time interval. Significant difference was found between group Ia+b (septic neonates) and group II for PCT and CRP at 24 and 48 h, but not for IL-8. There was no difference between group Ia+b and group III except for CRP at 24 h. Diagnostic accuracy was best for PCT on admission and for CRP at 24 h. Serum PCT and IL-8 are not specific markers for early severe bacterial infection in critically ill neonates and are not better than CRP.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Infant, Newborn; Interleukin-8; Protein Precursors; Respiratory Distress Syndrome, Newborn

The objective of this study was to determine the degree of leukocyte activation, as measured by cytokine release, in circulating blood during experimental extracorporeal circulation. Complete in vitro extracorporeal membrane oxygenation (ECMO) circuits were used, and 9 experiments were performed. Whole blood stored at 37 degrees C was used as the control. Blood samples were withdrawn before the start of perfusion and at 24 h of perfusion. Statistically significant releases of interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist were observed in the perfusion circuits compared to both the control blood and baseline values. Also, increases in plasma tumor necrosis factor (TNF)alpha and IL-6 were seen after 24 h of perfusion although these changes did not reach statistical significance. These results indicate that extracorporeal circulation induced leukocyte activation and cytokine release. These reactions might, as an additional trauma, deteriorate the situation in an already severely ill patient. A search for methods to counteract this untoward activation seems warranted.

Topics: Adult; Anticoagulants; Blood Cell Count; Chemotaxis, Leukocyte; Critical Illness; Cytokines; Equipment Design; Extracorporeal Circulation; Hemoglobins; Heparin; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Leukocyte Count; Leukocytes; Neutrophils; Oxygenators; Platelet Count; Receptors, Interleukin-1; Tumor Necrosis Factor-alpha