Lipopolysaccharide-binding protein for monitoring of postoperative sepsis: complemental to C-reactive protein or redundant?

INTRODUCTION: To prospectively evaluate the performance of Lipopolysaccharide-Binding Protein (LBP) in prediction of hospital mortality and its correlation to C-reactive Protein (CRP), we studied sixty consecutive, postoperative patients with sepsis admitted to the university hospital intensive care unit. MEASUREMENTS AND METHODS: Plasma LBP and CRP were serially measured from day(d)1 (onset of sepsis) to d14 in parallel with clinical data until d28. Predictive value and correlation of LBP and CRP were analyzed by Receiver Operating Characteristic (ROC) curve analysis and Pearson's test, respectively. MAIN RESULTS: LBP and CRP showed the highest levels on d2 or d3 after the onset of sepsis with no significant difference between survivors and nonsurvivors. Only at d7, nonsurvivors had significantly (p = .03) higher levels of CRP than survivors. Accordingly, in ROC analysis, concentration of CRP and LBP on d7 poorly discriminated survivors from nonsurvivors (area under curve = .62 and .55, respectively) without significant difference between LBP- and CRP-ROC curves for paired comparison. LBP and CRP plasma levels allocated to quartiles correlated well with each other (r(2) = .95; p = .02). Likewise, changes in plasma concentrations of LBP and CRP from one observation to the next showed a marked concordance as both parameters concomitantly increased or decreased in 76% of all cases. CONCLUSIONS: During the first 14 days of postoperative sepsis, LBP plasma concentrations showed a time course that was very similar to CRP with a high concordance in the pattern of day-to-day changes. Furthermore, like CRP, LBP does not provide a reliable clue for outcome in this setting.

Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis.

PURPOSE: To prospectively evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) as percentage of baseline (POB) in predicting hospital survival, we studied 64 consecutive, postoperative patients with severe sepsis. MATERIALS AND METHODS: Plasma PCT, IL-6, and CRP were serially measured from day 1 (onset of sepsis) to day 14 in parallel with clinical data until day 28. Multivariate logistic regression and univariate analysis of predictive accuracy of PCT-, IL-6-, and CRP-POB were performed. Newly derived binary prediction rules were evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: In survivors, PCT and IL-6 significantly decreased from days 1 to 14, whereas CRP did not. In nonsurvivors, the inflammation markers mostly increased within the second week. At day 7, logistic regression analysis revealed PCT-POB as an independent determinant for survival. Especially, PCT-POB not exceeding 50% and PCT-POB not exceeding 25% with CRP-POB not exceeding 75% on day 7 indicated a favorable outcome with a positive predictive value/sensitivity of 75%/97% and 92%/67%, respectively. In comparison, pretest likelihood to survive by day 28 and observed survival rate were 60% and 67%, respectively. CONCLUSIONS: Prediction rules of decrease in PCT-POB on day 7 in combination with CRP-POB may serve to monitor efficacy and guide duration of therapy in critically ill patients.

Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study.

BACKGROUND: Single-center trials have shown that monocytic HLA-DR is a good marker for monitoring the severity of temporary immunodepression after trauma, major surgery, or sepsis. A new test for measuring monocytic HLA-DR is now available. METHODS: We evaluated a new test reagent set for monocytic HLA-DR expression (BD Quantibritetrade mark HLA-DR/Monocyte reagent; Becton Dickinson) in single-laboratory and interlaboratory experiments, assessing preanalytical handling, lyse-no-wash (LNW) vs lyse-wash (LW) values, reference values, and the effect of use of different flow cytometers and different instrument settings on test variance. RESULTS: For preanalytical handling, EDTA anticoagulation, storage on ice as soon as possible, and staining within 4 h after blood collection gave results comparable to values obtained for samples analyzed immediately after collection (mean increase of approximately 4% in monocytic HLA-DR). Comparison of LNW and LW revealed slightly higher results for LNW ( approximately 18% higher for LNW compared with LW; r = 0.982). Comparison of different flow cytometers and instrument settings gave CVs <4%, demonstrating the independence of the test from these variables and suggesting that this method qualifies as a standardized test. CV values from the interlaboratory comparison ranged from 15% (blood sample unprocessed before transport) to 25% (stained and fixed before transport). CONCLUSIONS: For the BD Quantibrite HLA-DR/Monocyte test, preanalytical handling is standardized. Single-laboratory results demonstrated the independence of this test from flow cytometer and instrument settings. Interlaboratory results showed greater variance than single-laboratory values. This interlaboratory variance was partly attributable to the influence of transport and can be reduced by optimization of transport conditions.

Coincidence of pro- and anti-inflammatory responses in the early phase of severe sepsis: Longitudinal study of mononuclear histocompatibility leukocyte antigen-DR expression, procalcitonin, C-reactive protein, and changes in T-cell subsets in septic and postoperative patients.

OBJECTIVE: To determine the time course of histocompatibility leukocyte antigen (HLA)-DR expression in peripheral blood mononuclear cells and their relationship to markers of inflammation, organ function, and outcome during severe sepsis. DESIGN: Prospective, longitudinal study. SETTING: University hospital intensive care unit. PATIENTS: Twenty-three postoperative patients with severe sepsis and 26 patients with uneventful postoperative course as well as 24 healthy, age-matched subjects. INTERVENTIONS: Serum procalcitonin was determined by using an immunochemiluminescence assay, and C-reactive protein and leukocyte antigens were determined by using flow cytometry over 14 days in parallel with clinical data collection. MEASUREMENTS AND MAIN RESULTS: Despite a relative lymphopenia, absolute lymphocyte counts and CD4+/CD8+ T-cell ratio in septic patients were significantly elevated above normal. Particularly, CD4+ and CD8+ T-cell counts in nonsurvivors of sepsis were approximately twice as high as those of survivors. Significantly decreased monocytic HLA-DR expression was observed in both survivors and nonsurvivors at the onset of severe sepsis. Percentages of HLA-DR+ lymphocytes, however, were significantly increased during sepsis, especially in nonsurvivors. Whereas survivors of sepsis showed a continuous recovery of monocytic HLA-DR expression to >or=70% within 10 days, nonsurvivors were characterized by a second decrease in monocytic HLA-DR expression after day 7 or a permanent suppression (<40%). Peak of systemic inflammatory reaction, documented by maximum serum concentrations of procalcitonin and C-reactive protein, coincided with the nadir of monocytic HLA-DR expression. Moreover, procalcitonin and C-reactive protein as well as scores on the Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment were inversely correlated with the monocytic HLA-DR expression. CONCLUSIONS: Decreases in monocytic HLA-DR expression occurred simultaneously with signs of hyperinflammation as early as the onset of severe sepsis and usually developed in opposite directions than inflammatory markers and sepsis severity scores.