calca-protein--human and Shock--Septic

Procalcitonin (PCT) is an acute-phase reactant that has been used to diagnose and potentially track the treatment of sepsis. Procalcitonin values rise initially as the infection sets in and eventually fall with resolution. Its level has been reported to be significantly higher in potential nonsurvivors of a septic episode than among survivors. However, there is also a significant amount of evidence against this. We thus conducted a meta-analysis to pool data from all the available studies regarding PCT levels in survivors and nonsurvivors of sepsis. An extensive literature search was conducted using the key words "procalcitonin," "sepsis," and "prognosis." The references of the relevant studies were also scanned. The data from the eligible studies were extracted and analyzed for any significant pooled mean difference between survivors and nonsurvivors both on days 1 and 3. The mean difference in the day 1 PCT values between survivors and nonsurvivors was found to be statistically significant (P = 0.02). The mean difference on day 3 was also statistically significant (P = 0.002). However, in a subgroup consisting of studies on patients with severe sepsis and septic shock, day 1 difference was not found to be significant (P = 0.62). We found heterogeneity of 90% in our study population, which decreased to 62% after exclusion of studies conducted in emergency department patients. Procalcitonin levels in early stages of sepsis are significantly lower among survivors as compared with nonsurvivors of sepsis.

Topics: Acute-Phase Proteins; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic; Survival Analysis; Survivors; Time Factors

Patients in the intensive care unit (ICU) frequently receive prolonged or even unnecessary antibiotic therapy, which selects for antibiotic-resistant bacteria. Over the last decade there has been great interest in biomarkers, particularly procalcitonin, to reduce antibiotic exposure.. In this narrative review, we discuss the value of biomarkers and provide additional information beyond clinical evaluation in order to be clinically useful and review the literature on sepsis biomarkers outside the neonatal period. Both benefits and limitations of biomarkers for clinical decision-making are reviewed.. Several randomized controlled trials (RCTs) have shown the safety and efficacy of procalcitonin to discontinue antibiotic therapy in patients with severe sepsis or septic shock. In contrast, there is limited utility of procalcitonin for treatment initiation or withholding therapy initially. In addition, an algorithm using procalcitonin for treatment escalation has been ineffective and is probably associated with poorer outcomes. Little data from interventional studies are available for other biomarkers for antibiotic stewardship, except for C-reactive protein (CRP), which was recently found to be similarly effective and safe as procalcitonin in a randomized controlled trial. We finally briefly discuss biomarker-unrelated approaches to reduce antibiotic duration in the ICU, which have shown that even without biomarker guidance, most patients with sepsis can be treated with relatively short antibiotic courses of approximately 7 days.. In summary, there is an ongoing unmet need for biomarkers which can reliably and early on identify patients who require antibiotic therapy, distinguish between responders and non-responders and help to optimize antibiotic treatment decisions among critically ill patients. Available evidence needs to be better incorporated in clinical decision-making.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Decision Making; Humans; Predictive Value of Tests; Protein Precursors; Randomized Controlled Trials as Topic; Shock, Septic

To assess the clinical value of procalcitonin (PCT ) in the diagnosis of sepsis in adults.. An extensive search for related literature from the Wanfang data, CNKI, VIP, Medline/PubMed, Embase/OvidSP and the Cochrane Library up to December 2014 was performed. The articles, including prospective observational studies or randomized controlled trials, regarding PCT for the diagnosing of sepsis were enrolled. Only patients older than 18 years were included. Patients with sepsis, severe sepsis, or septic shock served as the experimental group, and those with a systemic inflammatory response syndrome (SIRS) of non-infectious origin as control group. The language of literature included was English or Chinese. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Heterogeneity, pooled diagnostic odds ratio (DOR), pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the summary receiver operating characteristic curve (SROC) and subgroup analysis were analyzed with the software of Metadisc 1.4.. A total of 6 385 published reports were collected, and among them 24 met the inclusion criteria, including a total. of 3 107 patients. The studies showed substantial heterogeneity (I2 = 69.4%), and random effect model was used for Meta analysis, showing that the pooled DOR was 10.37 [95% confidence interval (95%CI) = 7.10-15.17]. No evidence of a threshold effect was found (Spearman correlation coefficient = 0.27, calculated by logarithm of sensitivity and logarithm of 1-specificity, P = 0.20). The DOR values of pooled and each study were not distributed along the same line in forest plots, and Cochran-Q = 78.33, P = 0.000 0, showing that there was heterogeneity in result from non threshold effect. Except for partial heterogeneity caused by non threshold effect, the result of Meta regression analysis including PCT detection method, categories of disease, research location and so on showed P values were all higher than 0.05. Thus, the heterogeneity could not be explained by Meta regression analysis. The pooled sensitivity was 74% (95% CI = 72%-76%), the pooled specificity was 70% (95% CI = 67%-72%), the pooled positive likelihood ratio was 2.79 (95% CI = 2.31-3.38), the pooled negative likelihood ratio was 0.34 (95% CI = 0.28-0.41), and the pooled AUC was 0.83 (95% CI = 0.79-0.87). AUC in medical patients was 0.80 (95% CI = 0.75-0.85), which was higher than that in surgical patients [0.71 (95% CI = 0.65-0.81)].. Our results indicate a moderate degree of value of PCT for diagnosis of sepsis in adult patients. The diagnostic accuracy in medical patients is higher than that in surgical patients. PCT is a good auxiliary biomarker for diagnosis of sepsis.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Observational Studies as Topic; Prospective Studies; Protein Precursors; Randomized Controlled Trials as Topic; ROC Curve; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Procalcitonin (PCT) is used as a biomarker for the diagnosis of sepsis, severe sepsis and septic shock. At the same time, PCT has also been used to guide antibiotic therapy. This review outlines the main indications for PCT measurement and points out possible pitfalls. The classic indications for PCT measurement are: (i) confirmation or exclusion of diagnosis of sepsis, severe sepsis, or septic shock, (ii) severity assessment and follow up of systemic inflammation mainly induced by microbial infection, and (iii) individual, patient adapted guide of antibiotic therapy and focus treatment. Using serially monitored PCT levels, the duration and need of antibiotic therapy can be better adapted to the individual requirements of the patient. This individualized approach has been evaluated in various studies, and it is recommended to be a part of an antibiotic stewardship program.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis; Severity of Illness Index; Shock, Septic

Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing.. Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org. Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus.. Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis. Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups. Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups.. Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care. Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Administration Schedule; Glycoproteins; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Protein Precursors; Sepsis; Shock, Septic

Sepsis is a clinical syndrome defined by physiologic changes indicative of systemic inflammation, which are likely attributable to documented or suspected infection. Septic shock is the progression of those physiologic changes to the extent that delivery of oxygen and metabolic substrate to tissues is compromised. Biomarkers have the potential to diagnose, monitor, stratify and predict outcome in these syndromes. C-reactive protein is elevated in inflammatory and infectious conditions and has long been used as a biomarker indicating infection. Procalcitonin has more recently been shown to better distinguish infection from inflammation. Newer candidate biomarkers for infection include IL-18 and CD64. Lactate facilitates the diagnosis of septic shock and the monitoring of its progression. Multiple stratification biomarkers based on genome-wide expression profiling are under active investigation and present exciting future possibilities.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Infections; Inflammation; Interleukin-18; Lactates; Protein Precursors; Receptors, IgG; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Procalcitonin may be associated with reduced antibiotic usage compared to usual care. However, individual randomized controlled trials testing this hypothesis were too small to rule out harm, and the full cost-benefit of this strategy has not been evaluated. The purpose of this analysis was to evaluate the effect of a procalcitonin-guided antibiotic strategy on clinical and economic outcomes.. The use of procalcitonin-guided antibiotic therapy.. We searched computerized databases, reference lists of pertinent articles, and personal files. We included randomized controlled trials conducted in the intensive care unit that compared a procalcitonin-guided strategy to usual care and reported on antibiotic utilization and clinically important outcomes. Results were qualitatively and quantitatively summarized. On the basis of no effect in hospital mortality or hospital length of stay, a cost or cost-minimization analysis was conducted using the costs of procalcitonin testing and antibiotic acquisition and administration. Costs were determined from the literature and are reported in 2009 Canadian dollars. Five articles met the inclusion criteria. Procalcitonin-guided strategies were associated with a significant reduction in antibiotic use (weighted mean difference -2.14 days, 95% confidence interval -2.51 to -1.78, p < .00001). No effect was seen of a procalcitonin-guided strategy on hospital mortality (risk ratio 1.06, 95% confidence interval 0.86-1.30, p = .59; risk difference 0.01, 95% confidence interval -0.04 to +0.07, p = .61) and intensive care unit and hospital lengths of stay. The cost model revealed that, for the base case scenario (daily price of procalcitonin Can$49.42, 6 days of procalcitonin measurement, and 2-day difference in antibiotic treatment between procalcitonin-guided therapy and usual care), the point at which the cost of testing equals the cost of antibiotics saved is when daily antibiotics cost Can$148.26 (ranging between Can$59.30 and Can$296.52 on the basis of different assumptions in sensitivity analyses).. Procalcitonin-guided antibiotic therapy is associated with a reduction in antibiotic usage that, under certain assumptions, may reduce overall costs of care. However, the overall estimate cannot rule out a 7% increase in hospital mortality.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Humans; Protein Precursors; Shock, Septic; Time Factors; Treatment Outcome

Prompt diagnosis, intervention, and risk assessment are critical in caring for septic patient but remain difficult with currently available methods. Biomarkers may become useful adjuncts to clinicians and ultimately serve as targets for future therapeutic trials in sepsis. The most relevant markers are reviewed in this article, including interleukin-6, C-reactive protein, procalcitonin, triggering receptor expressed on myeloid cells-1, and biomarker panels.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Interleukin-6; Macrophages; Membrane Glycoproteins; Monocytes; Neutrophils; Predictive Value of Tests; Prognosis; Protein Precursors; Receptors, Immunologic; Risk Assessment; Sepsis; Shock, Septic; Triggering Receptor Expressed on Myeloid Cells-1

To quantify the accuracy of serum procalcitonin as a diagnostic test for sepsis, severe sepsis, or septic shock in adults in intensive care units or after surgery or trauma, alone and compared with C-reactive protein. To draw and compare the summary receiver operating characteristics curves for procalcitonin and C-reactive protein from the literature.. MEDLINE (keywords: procalcitonin, intensive care, sepsis, postoperative sepsis, trauma); screening of the literature.. Meta-analysis of all 49 published studies in medical, surgical, or polyvalent intensive care units or postoperative wards. Children, medical patients, and immunocompromised patients were excluded.. Thirty-three studies fulfilled inclusion criteria (3,943 patients, 1,828 males, 922 females; mean age: 56.1 yrs; 1,825 patients with sepsis, severe sepsis, or septic shock; 1,545 with only systemic inflammatory response syndrome); eight studies could not be analyzed statistically. Global mortality rate was 29.3%.. Global odds ratios for diagnosis of infection complicated by systemic inflammation were 15.7 for the 25 studies (2,966 patients) using procalcitonin (95% confidence interval, 9.1-27.1) and 5.4 for the 15 studies (1,322 patients) using C-reactive protein (95% confidence interval, 3.2-9.2). The summary receiver operating characteristics curve for procalcitonin was better than for C-reactive protein. In the 15 studies using both markers, the Q* value (intersection of summary receiver operating characteristics curve with the diagonal line where sensitivity equals specificity) was significantly higher for procalcitonin than for C-reactive protein (0.78 vs. 0.71, p = .02), the former test showing better accuracy.. Procalcitonin represents a good biological diagnostic marker for sepsis, severe sepsis, or septic shock, difficult diagnoses in critically ill patients. Procalcitonin is superior to C-reactive protein. Procalcitonin should be included in diagnostic guidelines for sepsis and in clinical practice in intensive care units.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Humans; Male; Middle Aged; Postoperative Complications; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Wounds and Injuries

Despite advances in the diagnosis and treatment of infections diseases, sepsis and ensuing multiorgan failure are the major causes of morbidity and mortality in the intensive care units. Such manifestations of systemic inflammation as fever, leukocytosis, tachycardia, etc. may be noninfectious in origin and are neither specific nor sensitive for sepsis. Procalcitonin is a new potential marker for detection of bacterial, fungal and protozoal infections. Procalcitonin, a propeptide of calcitonin, is normally produced in the C-cells of the thyroid gland. Procalcitonin is a polypeptide consisting of 116 amino acids and with a molecular weight of about 13 kDa. During severe systemic infections it is produced by extrathyroidal tissues. Procalcitonin can be put to immediate use in both diagnostic and therapeutic decision-making. This review article discusses biology of procalcitonin, its laboratory determination, usage as an indicator for severe infection and sepsis, and comparison with circulating cytokines in severe infection. It also reviews value of procalcitonin in differentiation of infectious vs non-infectious inflammatory host response, possible elevation of procalcitonin in the absence of infection, its use for differentiation of viral and non-viral infections and as marker for prognosis and evaluation of therapy. Specific indications for determination of procalcitonin are also discussed.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chromatography; Cytokines; Diagnosis, Differential; Humans; Intensive Care Units; Luminescence; Prognosis; Protein Precursors; Sensitivity and Specificity; Shock, Septic; Systemic Inflammatory Response Syndrome

Early diagnosis of the different severities of septic inflammation is important for early implementation of specific therapies. Sepsis and severe sepsis are accompanied by clinical and laboratory signs of systemic inflammation. However, patients suffering from non-infectious inflammation may present with similiar signs and symptoms making it difficult to diagnose infection based on clinical findings alone. Bacteriological evidence of sepsis, though definitive and specific, may not be obtainable, is time-consuming and even may not occur concurrently with clinical signs of sepsis. It is therefore important to identify markers, which, by enabling an early diagnosis of sepsis and organ dysfunction, would allow early specific therapeutic interventions. Wheras C-reactive Protein is a more sensitive parameter for the diagnosis of non-systemic infections, Procalcitonin seems to be a useful parameter to improve the diagnosis and monitoring of therapy in patients with severe sepsis and septic shock.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Prognosis; Protein Precursors; Shock, Septic; Systemic Inflammatory Response Syndrome

Procalcitonin is a polypeptide present in the plasma of healthy subjects in minimal levels (< 0.5 ng/ml). Serum procalcitonin is markedly increased a few hours after the administration of endotoxin to human volunteers and in invasive bacterial infection (sepsis, septic shock, meningitis). Procalcitonin is moderately increased in local bacterial infection (pneumonia pyelonephritis) and is unchanged in viral infections or bacterial colonization. Procalcitonin is increased in serious bacterial infections in neonates, children and adults and is currently the best diagnostic marker of severe bacterial infection, being better than leukocyte, interleukin or C-reactive protein counts. C-reactive protein levels can be normal in severe sepsis and some viral infections. We studied 54 children with sepsis in whom plasma procalcitonin levels showed a positive correlation with the vasoactive drugs necessary to maintain cardiovascular activity. The semiquantitative procalcitonin test is simple and easy to use at the bedside at any time and in any hospital as no instruments are required. Within 30 minutes, the test identifies the type of infection and whether antibiotics are indicated.

Topics: Adult; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Humans; Meningitis, Bacterial; Protein Precursors; Sepsis; Shock, Septic

Topics: Adult; Age Factors; Animals; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Glycoproteins; Humans; Infant; Infant, Newborn; Prospective Studies; Protein Precursors; Shock, Septic

Sepsis is a major cause of mortality and morbidity in critically ill patients. Procalcitonin (PCT) and C-reactive protein (CRP) are the most frequently used biomarkers in sepsis. We investigated changes in PCT and CRP concentrations in critically ill patients with sepsis to determine which biochemical marker better predicts outcome. We retrospectively analyzed 171 episodes in 157 patients with severe sepsis and septic shock who were admitted to the Samsung Medical Center intensive care unit from March 2013 to February 2014. The primary endpoint was patient outcome within 7 days from ICU admission (treatment failure). The secondary endpoint was 28-day mortality. Severe sepsis was observed in 42 (25%) episodes from 41 patients, and septic shock was observed in 129 (75%) episodes from 120 patients. Fifty-five (32%) episodes from 42 patients had clinically-documented infection, and 116 (68%) episodes from 99 patients had microbiologically-documented infection. Initial peak PCT and CRP levels were not associated with treatment failure and 28-day mortality. However, PCT clearance (PCTc) and CRP (CRPc) clearance were significantly associated with treatment failure (p = 0.027 and p = 0.030, respectively) and marginally significant with 28-day mortality (p = 0.064 and p = 0.062, respectively). The AUC for prediction of treatment success was 0.71 (95% CI, 0.61-0.82) for PCTc and 0.71 (95% CI, 0.61-0.81) for CRPc. The AUC for survival prediction was 0.77 (95% CI, 0.66-0.88) for PCTc and 0.77 (95% CI, 0.67-0.88) for CRPc. Changes in PCT and CRP concentrations were associated with outcomes of critically ill septic patients. CRP may not be inferior to PCT in predicting outcome in these patients.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Disease-Free Survival; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Severity of Illness Index; Shock, Septic; Survival Rate

Serum procalcitonin is commonly used to differentiate systemic inflammation due to infection from non-infectious causes. Limited data exist on the value of procalcitonin in predicting relative adrenal insufficiency (RAI). This study evaluated the value of procalcitonin in predicting RAI and mortality in cirrhotic patients with septic shock.. This was a post-hoc analysis of a randomized placebo-controlled trial that evaluated low-dose hydrocortisone in cirrhotic patients with septic shock. Extracted first study-day data included serum procalcitonin, baseline serum cortisol, cortisol level after 250 microg - adrenocorticotropic hormone stimulation test and 28 - day mortality. RAI was defined as a baseline serum cortisol < 10 microg/dL or cortisol not rising by > 9 microg/dL after stimulation. Procalcitonin > 0.5 ng/mL was considered high.. Forty-five patients had serum procalcitonin measured (mean = 2.7 +/- 3.2 ng/mL, first and third quartiles were 0.3 and 3.3 ng/mL, respectively). Most (78%) patients had high procalcitonin levels. RAI was present in 34 (76%) patients. Patients with high procalcitonin were more likely to have RAI (odds ratio, 4.8; 95% confidence interval, 1.1 - 22.1). Receiver operator characteristic curve analysis showed that the best cut-off for detecting RAI was 1.0 ng/mL (sensitivity = 79% and specificity = 55%). High serum procalcitonin was not associated with 28 -day mortality (80% for normal procalcitonin and 77% for high procalcitonin, p = 0.61).. High serum procalcitonin was highly associated with RAI in cirrhotic patients with septic shock. Procalcitonin was not associated with 28 - day mortality in this patient population.

Topics: Adrenal Insufficiency; Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Hydrocortisone; Liver Cirrhosis; Male; Middle Aged; Placebos; Protein Precursors; Shock, Septic; Treatment Outcome

The aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment.. In total, 116 patients with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models.. Presepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC.. In patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment.. ClinicalTrials.gov http://NCT01535534. Registered 14 February 2012.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Humans; Intensive Care Units; Interleukin-6; Leukocyte Count; Lipopolysaccharide Receptors; Male; Middle Aged; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Time Factors

To investigate the value of timing of antibiotics in pediatric septic shock.. Eighty children with septic shock treated with bundle treatment in Department of Critical Care Medicine were retrospectively analyzed. Eighty children with septic shock were divided into observation group (n=40, anti-infection therapy within 1 hour after admission) and control group (n=40, anti-infection therapy 1-6 hours after admission). The contents of lactate, C-reaction protein (CRP) and procalcitonin (PCT) were compared between two groups at admission and 24 hours and 72 hours after admission.. Lactate in the observation group was significantly lower than that of the control group within the first 24 hours after admission (8.65 ± 2.84 mmol/L vs. 11.75 ± 3.20 mmol/L, P<0.01). CRP in the observation group was significantly lower than that of the control group 24 hours and 72 hours after admission (66.25 ± 8.55 mg/L vs. 91.77 ± 7.71 mg/L, 22.03 ± 7.46 mg/L vs. 50.11 ± 7.30 mg/L, both P<0.01). PCT in the observation group was significantly lower than that of the control group 72 hours after admission (0.67 ± 0.31 μg/L vs. 1.16 ± 0.25 μg/L, P<0.01). Time for shock recovery in the observation group was significantly shorter than that of the control group (6.80 ± 3.70 hours vs. 12.80 ± 3.63 hours, P<0.05), but no statistical difference in mortality rate between groups was found [5% (2/40) vs. 10% (4/40), P>0.05].. With the early empirical anti-infection treatment in pediatric septic shocked patients, time for recovery from shock can be shortened and successful rate of resuscitation can be improved.

Topics: Anti-Bacterial Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Care; Female; Humans; Infant; Lactic Acid; Male; Prognosis; Protein Precursors; Shock, Septic; Time Factors

The aims of the present study were to evaluate the prognostic value of adrenomedullin (AM) in septic patients in the emergency department (ED) and to compare it with procalcitonin (PCT) and Mortality in Emergency Department Sepsis (MEDS) score.. We enrolled 837 consecutive patients who fulfilled the systemic inflammatory response syndrome criteria and were admitted to the ED of Beijing Chaoyang Hospital and 100 age-matched healthy controls. Serum AM and PCT were determined, and MEDS score was calculated at enrollment. The prognostic value of AM was compared with PCT and MEDS score. Primary outcome was in-hospital mortality.. On admission, mean levels of AM were 28.66 ± 6.05 ng/L in 100 healthy controls, 31.65 ± 6.47 ng/L in 153 systemic inflammatory response syndrome patients, 33.24 ± 8.59 ng/L in 376 sepsis patients, 34.81 ± 8.33 ng/L in 210 severe sepsis patients, and 45.15 ± 9.87 ng/L in 98 septic shock patients. The differences between the 2 groups were significant. Adrenomedullin level was higher in nonsurvivors than in survivors in every group. The area under receiver operating characteristic curve of AM for predicting in-hospital mortality in septic patients was 0.773, which was better than PCT (0.701) and MEDS score (0.721). Combination of AM and MEDS score improved the accuracy of AM and MEDS score in predicting the risk of in-hospital mortality (area under receiver operating characteristic curve, 0.817). In logistic regression analysis, AM and MEDS score were independent predictors of in-hospital mortality.. Adrenomedullin is valuable for prognosis in septic patients in the ED.

Topics: Adrenomedullin; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Prognosis; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Shock, Septic; Systemic Inflammatory Response Syndrome

Biomarkers such as procalcitonin (PCT) have been studied to guide duration of antibiotic therapy. We aimed to assess whether a decrease in PCT levels could be used to reduce the duration of antibiotic therapy in intensive care unit (ICU) patients with a proven infection without risking a worse outcome. We assessed 265 patients with suspected sepsis, severe sepsis, or septic shock in our ICU. Of those, we randomized 81 patients with a proven bacterial infection into 2 groups: an intervention group in which the duration of the antibiotic therapy was guided by a PCT protocol and a control group in which there was no PCT guidance. In the per-protocol analysis, the median antibiotic duration was 9 days in the PCT group (n = 20) versus 13 days in the non-PCT group (n = 31), P = 0.008. This study demonstrates that PCT can be a useful tool for limiting antimicrobial therapy in ICU patients with documented bacterial infection.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cost Savings; Female; Humans; Male; Middle Aged; Protein Precursors; Shock, Septic; Treatment Outcome

We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis.. Randomized open clinical trial.. Two university hospitals in Brazil.. Patients with severe sepsis or septic shock.. Patients were randomized in two groups: the procalcitonin group and the C-reactive protein group. Antibiotic therapy was discontinued following a protocol based on serum levels of these markers, according to the allocation group. The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25% shorter than in the C-reactive protein group. For both groups, at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and/or bacteremia at inclusion, and patients with evident resolution of the infectious process had antibiotics stopped after 7 days, despite biomarkers levels.. Ninety-four patients were randomized: 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group. The mean age was 59.8 (SD, 16.8) years. The median duration of antibiotic therapy for the first episode of infection was 7.0 (Q1-Q3, 6.0-8.5) days in the procalcitonin group and 6.0 (Q1-Q3, 5.0-7.0) days in the C-reactive protein group (p=0.13), with a hazard ratio of 1.206 (95% CI, 0.774-1.3; p=0.13). Overall, protocol overruling occurred in only 13 (13.8%) patients. Twenty-one patients died in each group (p=0.836).. C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients, causing no apparent harm.

Topics: Aged; Anti-Bacterial Agents; Biomarkers; Brazil; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Confidence Intervals; Female; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Outcome Assessment, Health Care; Protein Precursors; Shock, Septic

: The lack of specific clinical manifestations for sepsis frequently leads to delayed diagnosis. Identification of sensitive and specific indicators that can be easily assessed, accurately reflect infection severity and prognosis and are clinically important in the differential diagnosis of sepsis, is of great significance. The purpose of this study was to evaluate the diagnostic and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in high selected, mostly postoperative patients with suspicion of sepsis.. : Fifty-two consecutive patients hospitalized in a surgical intensive care unit with suspicion of infection included 14 patients with systemic inflammatory response syndrome (SIRS), 9 patients with sepsis, 14 patients with severe sepsis and 15 patients with septic shock. Within 12 hours after enrollment, plasma levels of sTREM-1, procalcitonin (PCT), tumor necrosis factor (TNF)-α, interleukin-6 and C-reactive protein were measured and compared between subgroups to elucidate their diagnostic and prognostic values.. : Plasma sTREM-1 levels were higher in patients with sepsis than in patients with SIRS (111.7 versus 64.1 pg/mL, P < 0.05), with sensitivity, specificity and a predictive value higher than those of PCT and TNF-α. Plasma sTREM-1 levels were significantly different between the sepsis, severe sepsis and septic shock subgroups (P < 0.001). For the receiver operating characteristic for predicting death, the area under the curve of sTREM-1 was 0.861, similar to that of TNF-α, blood lactate and PCT (0.848, 0.719 and 0.706, respectively).. : In postoperative patients, plasma levels of sTREM-1 and TNF-α could differentiate sepsis from SIRS. sTREM levels also reflected the severity of sepsis and were noninferior for prognosis compared with other biochemical indexes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Diagnosis, Differential; Female; Humans; Intensive Care Units; Lactic Acid; Male; Membrane Glycoproteins; Middle Aged; Postoperative Complications; Prognosis; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Shock, Septic; Systemic Inflammatory Response Syndrome; Time Factors; Triggering Receptor Expressed on Myeloid Cells-1; Tumor Necrosis Factor-alpha

This study evaluates the potential prognostic value of serial measurements of different biomarkers (procalcitonin [PCT], C-reactive protein and leukocytes [CRP]) in septic shock patients.. Prospective observational study.. Intensive care unit of a third-level University Hospital.. The study comprised a total of 88 septic shock patients defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria. The PCT, CRP and leukocytes were recorded on admission to the ICU and again 72 hours after admission.. None.. Those patients with increasing procalcitonin levels showed higher hospital mortality than those with a decreasing levels (58.8% vs. 15.4%, P<0.01). No such effect was observed in relation to C-reactive protein or leukocytes. The best area under the curve for prognosis was for procalcitonin clearance (0.79). A procalcitonin clearance of 70% or higher offered a sensitivity and specificity of 94.7% and 53%, respectively.. Serial procalcitonin measurements are more predictive of the prognosis of septic shock patients than single measurements of this parameter. The prognostic reliability of the latter is also better than in the case of C-reactive protein and leukocytes. The application of serial procalcitonin measurements may allow the identification of those septic patients at increased mortality risk, and help improve their treatment.

Topics: Aged; Aged, 80 and over; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Comorbidity; Diagnosis-Related Groups; Female; Hospital Mortality; Hospitals, University; Humans; Intensive Care Units; Leukocyte Count; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Risk; ROC Curve; Sensitivity and Specificity; Shock, Septic

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) controls tryptophan metabolism and is induced by pro-inflammatory stimuli. We investigated whether immunostimulatory treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) influences IDO activity and tryptophan metabolism in sepsis. Thirty-six patients with severe sepsis/septic shock and sepsis-associated immunosuppression (assessed using monocytic human leukocyte antigen-DR (mHLA-DR) expression) were assessed in a controlled trial of GM-CSF or placebo treatment for 8 days. Using tandem mass spectrometry, levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid, 5-hydroxytryptophan, serotonin, and estimated IDO activity were determined in a blinded fashion over a 9-day interval. At baseline, tryptophan and metabolite levels did not differ between the study groups. Although tryptophan levels were unchanged in both groups over the treatment interval (all p>0.8), IDO activity was markedly reduced after GM-CSF treatment (35.4 +/- 21.0 vs 21.6 +/-9.9 (baseline vs day 9), p = 0.02). IDO activity differed significantly between the 2 groups after therapy (p = 0.03). Metabolites downstream of IDO (kynurenine, quinolinic acid, kynurenic acid) were all induced in sepsis and declined in the GM-CSF group, but not in controls. Serotonin pathway metabolites remained unchanged in both groups (all p>0.15). Moreover, IDO activity correlated with procalcitonin (p< 0.0001, r = 0.56) and mHLA-DR levels (p = 0.005, r = -0.28) in the overall samples group. Thus, GM-CSF therapy is associated with decreased IDO activity and reduced kynurenine pathway catabolites in sepsis. This may be due to an improved antibacterial defence.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Granulocyte-Macrophage Colony-Stimulating Factor; HLA-DR Antigens; Humans; Immunologic Factors; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenic Acid; Kynurenine; Male; Middle Aged; Placebos; Protein Precursors; Quinolinic Acid; Sepsis; Serotonin; Shock, Septic; Treatment Outcome; Tryptophan

In cardiac acute patients, data on procalcitonin (PCT) are controversial and the clinical interpretation of absolute PCT values represents a major challenge since they may be influenced by several factors. No data are so far available on the dynamics of PCT levels in patients with cardiogenic shock.. to evaluate the serum evolution of PCT during intensive cardiac care unit (ICCU) staying in a group of 24 patients with cardiogenic shock (CS) following ST-elevation myocardial infarction (STEMI) submitted to primary percutaneous intervention (PCI) with no laboratory or clinical sign of infection. Furthermore we assessed the kinetics of PCT in a series of 24 patients with septic shock.. In septic shock, no significant difference was detectable in PCT kinetics between survivors (R2 = 0.90; P = 0.051) and non-survivors (R2 = 0.63; P = 0.204). In cardiogenic shock, survivors exhibited a significant reduction in PCT values (R2 = 0.94; P = 0.032) while non survivors did not (R2 = 0.68; P = 0.178).. differently from septic shock, cardiogenic shock following STEMI was associated with heterogeneous patterns of temporal PCT variations since only patients who survived exhibited a significant PCT reduction during ICCU stay. Our findings support the contention that the 'dynamic' approach may be more reliable that the static one especially in cardiogenic shock.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Electrocardiography; Female; Humans; Intensive Care Units; Male; Middle Aged; Myocardial Infarction; Protein Precursors; Shock, Cardiogenic; Shock, Septic; Survival Analysis

Diagnosis/grading of infection and the systemic response to infection may be difficult on admission to the intensive care unit, but it is even more complicated for severely ill patients with long intensive care stays. The ACCP-SCCM criteria are difficult to apply for such patients, and objective, validated biomarkers would be of great use in this setting.. Long-term (>6 days) critically ill patients in the general ICU of University Hospital were prospectively enrolled in the study. All patients were assessed daily by the attending physician using the ACCP-SCCM classification. C-reactive protein (CRP, mg/dL), procalcitonin (PCT, ng/mL), and interleukin-6 (IL-6, pg/mL) of daily stored sera were measured after each patient's discharge. After discharge, an independent, overall clinical evaluation and an a posteriori ACCP-SCCM classification were chosen as the reference standard for all comparisons. The assessor was aware of the patient's clinical course but was blinded to levels of biomarkers.. We studied clinical variables and biomarkers of 26 patients over a total of 592 patient days. The day-by-day ACCP-SCCM classification of the attending physician overestimated the severity of the inflammatory response to infection. The diagnostic discriminative ability of severe-sepsis/septic-shock for PCT was high (ROC area 0.952 [0.931-0.973]) and had a best threshold value of 1.58 (83.7% sensitivity, 94.6 % specificity). IL-6 had better discriminative ability than CRP, but both were worse than PCT.. PCT > 0.43 ng/mL could add to the clinical propensity for sepsis vs. SIRS not related to infection. Values higher than 1.58 ng/mL may support the bedside clinical diagnosis of severe-sepsis. PCT between 0.5 and 1.0 suggest tight daily monitoring of clinical conditions and re-evaluation of PCT.

Topics: Aged; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Decision Making; Diagnosis, Differential; Female; Hospitals, University; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Shock, Septic; Single-Blind Method; Systemic Inflammatory Response Syndrome

The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.. To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.. Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).. Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.

Topics: Aged; Aged, 80 and over; Algorithms; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Protocols; Critical Illness; Female; Glycoproteins; Humans; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Protein Precursors; Recurrence; Sepsis; Shock, Septic

Measurement of procalcitonin (PCT) has been studied for several years in infectious diseases. Some studies have focused on community-acquired pneumonia (CAP) but only one was conducted in critically ill patients hospitalized in an intensive care unit (ICU).. To determine the diagnostic and prognostic role of PCT in patients admitted in an intensive care unit for severe CAP, 110 patients hospitalized in our unit were prospectively studied. Within 48 hours following ICU admission, PCT serum level was measured with a quantitative method above a threshold value of 0.5 ng/ml.. Initially focusing on the diagnostic value of PCT, 20% of the patients had a serum PCT level <0.5 ng/ml, 30% between 0.5 ng/ml and 2 ng/ml, and 50%>/=2 ng/ml. Serum PCT level was higher in microbiologically documented CAP (median=4.9 ng/ml vs 1.5 ng/ml if no bacteria were found; p=0.001), but was not predictive of any specific bacterial agent. Concerning the prognostic value, the serum PCT level was higher for bacteremic patients and/or septic shock patients (4.9 ng/ml vs 1.5 ng/ml; p=0.0003). Moreover, PCT levels were increased in patients who developed, during their ICU stay, infection-related complications (septic shock, multiorgan dysfunction, acute respiratory distress syndrome and disseminated intravascular coagulation). Finally, the initial PCT level was significantly higher in patients who died during the ICU stay (5.6 ng/ml vs 1.5 ng/ml; p<0.0001). Such a relationship was not found with C-reactive protein (CRP).. In ICU patients admitted for severe CAP, initial PCT values could be an interesting predictor for complications and mortality.

Topics: Adult; Aged; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Critical Illness; Diagnosis, Differential; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Shock, Septic

The diagnosis of sepsis in critically ill patients is challenging because traditional markers of infection are often misleading. The present study was conducted to determine the procalcitonin level at early diagnosis (and differentiation) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, in comparison with C-reactive protein, IL-2, IL-6, IL-8 and tumour necrosis factor-alpha.. Thirty-three intensive care unit patients were diagnosed with SIRS, sepsis or septic shock, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. Blood samples were taken at the first and second day of hospitalization, and on the day of discharge or on the day of death. For multiple group comparisons one-way analysis of variance was applied, with post hoc comparison. Sensitivity, specificity and predictive values of PCT and each cytokine studied were calculated.. PCT, IL-2 and IL-8 levels increased in parallel with the severity of the clinical condition of the patient. PCT exhibited a greatest sensitivity (85%) and specificity (91%) in differentiating patients with SIRS from those with sepsis. With respect to positive and negative predictive values, PCT markedly exceeded other variables.. In the present study PCT was found to be a more accurate diagnostic parameter for differentiating SIRS and sepsis, and therefore daily determinations of PCT may be helpful in the follow up of critically ill patients.

Topics: Adult; Aged; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

Our objective is to analyze whether the combination of C-reactive protein (CRP), procalcitonin (PCT), presepsin or SCD14-ST and mid-regional pro-adrenomedullin (MR-proADM) measured in the first 24 h from ICU admission allowing a better management of septic patients (diagnostic and prognostic) both in severe sepsis (SS) and septic shock (SSh).. Cohort study of 388 patients admitted in the ICU during 12 months of whom 142 were controls. Biomarkers were measured through immunoluminometric assays in samples of serum or plasma within the first 24 h after admission. Data were evaluated with non-parametric statistics bivariant, ROC curve analysis for diagnostic evaluation and multivariate analyses for survival analysis.. In the analyzed cohort, 61.8% of patients were males, mean age: 63 years range (18-90) and 67.8% in controls mean age: 63 years, range (39-91). PCT showed the highest area under the curve (AUC) (0.989) as compared with the rest of biomarkers (p<0.01). PCT also enabled the difference between Gram-positive or Gram-negative bacteria to be determined. The AUCs for CRP (0.922) and presepsin (0.948) showed a similar diagnostic value. In cases of SSh, the AUC of presepsin experienced a noticeable increase (p<0.0001). MR-proADM showed a better prognostic value (p=0.00022) particularly in cases of SSh (p=0.00001) increasing along with the APACHE-II score.. PCT, MR-proADM and presepsin are complementary markers that could be of great help in the management of septic patients when they are measured in the first 24 h after ICU admission.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Immunologic Techniques; Lipopolysaccharide Receptors; Luminescent Measurements; Male; Middle Aged; Multivariate Analysis; Peptide Fragments; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Survival Analysis; Young Adult

This study aims to assess the diagnostic and prognostic value of endocan in patients with severe sepsis or septic shock on a medical intensive care unit (ICU).. 150 patients suspected for at least severe sepsis were enrolled on a medical ICU. On days 1, 3, and 8, plasma levels of endocan, procalcitonin (PCT), and interleukin (IL)-6 were measured. Follow-up on all-cause mortality was performed after 30 days and 6 months.. Endocan correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score II (SAPS II) (P < .006). Endocan was higher in patients with at least severe sepsis compared with systemic inflammatory response syndrome (SIRS) or sepsis patients (P = .0006) on days 1, 3, and 8. With a minimum sensitivity of 70%, uniform cutoff levels were set for ≥ sepsis at 1.8 ng/mL, for ≥ severe sepsis at 2.6 ng/mL, for ≥ septic shock at 2.9 ng/mL. On day 1, endocan levels of the fourth quartile were significantly associated with 30-days and 6-months mortality compared to lower levels. After adjustment in Cox regressions, endocan still revealed prognostic value.. Endocan showed diagnostic capacity to diagnose patients with severe sepsis and septic shock and revealed prognostic information for 30-days and 6-months all-cause mortality.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Male; Middle Aged; Neoplasm Proteins; Predictive Value of Tests; Prognosis; Protein Precursors; Proteoglycans; Regression Analysis; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Severe sepsis, septic shock and bacteremia are critical illnesses, and patients with these conditions require close monitoring and immediate medical treatment. Any delay in diagnosis may lead to an increase in mortality in such critically ill patients. Serum procalcitonin (PCT) has emerged as a highly accurate biomarker for differentiating sepsis from other non-infectious triggers.. In this study, we investigated the effectiveness of PCT in obtaining early diagnosis and efficient prognosis for such patients at the Emergency Department of Rajavithi Hospital.. A prospective study was performed of 110 adult patients who attended the emergency service department between August 1 2013 and October 31 2013. The effectiveness of PCT as a specific blood test analysis tool for detecting and classifying the severity of patients with sepsis was investigated, and sensitivity, specificity, negative predictive values (NPV), positive predictive values (PPV) and positive likelihood ratio (LR+) were used to differentiate infected patients.. One hundred and ten patients were enrolled and classified into 3 categories as follows: severe sepsis (n = 34, 30.9%), septic shock (n = 13, 11.8%), and bacteremia (n = 23, 20.9%). At a PCT level of ≥ 2 ng/dL, it was feasible to categorize patients as having severe sepsis (p < 0.001; RR 3.58; 95% CI 2.18-5.89), septic shock (p = 0.001; 5.73; 2.06- 15.93) or bacteremia (p < 0.001; 3.91; 1.98-7.73). Moreover, the PCT value yielded the following diagnostic performances for patients with: severe sepsis (PPV 70.8%; NPV 80.2%; LR+ 5.0; sensitivity 50.0%; specificity 90.8%); septic shock (33.3%; 94.2%; 3.6; 61.5%; 83.5%); and bacteremia (50.0%; 87.2%; 3.7; 52.2%; 86.2%).. PCT can be usefully employed as a promising chemical biomarker to differentiate the severity of infections in critically ill patients. Used together with clinical data, the PCT value of ≥ 2 ng/dL is efficient in categorizing such patients as having severe sepsis, septic shock or bacteremia.

Topics: Adult; Aged; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

The purpose of the study is to compare the clearance of procalcitonin (PCT-c) in the first 24 and 48 hours of treatment of severe sepsis and septic shock with another early prognostic marker represented by the 48-hour Δ Sequential Organ Failure Assessment (SOFA).. Prospective, observational cohort study conducted in a general intensive care unit including patients with severe sepsis and septic shock. The PCT-c was determined at the diagnosis of sepsis and after 24 and 48 hours. The SOFA score was determined at the time of intensive care unit admission and after 48 hours.. One hundred thirty adult patients with severe sepsis and septic shock were studied over an 18-month period. The 24- and 48-hour PTC-c scores were significantly higher in survivors (P < .0001). In nonsurvivors, the initial SOFA was significantly higher, and the 48-hour Δ SOFA was significantly smaller (P = .01). The area under the receiver operating characteristic curve was 0.68 for Δ SOFA and 0.76 for 24- and 48-hour PCT-c.. The 48-hour Δ SOFA score and the clearance of 24- and 48-hour PCT are useful markers of prognosis in patients with severe sepsis and septic shock. A decrease in PCT-c in the first 24 hours of treatment should prompt the reassessment of the appropriateness and adequacy of treatment.

Topics: Adult; Aged; Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Male; Middle Aged; Organ Dysfunction Scores; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Survivors; Time Factors

Sepsis is among the most common causes of death in hospitalized patients, and early recognition followed by immediate initiation of therapy is an important concept to improve survival in these patients. According to the definition of sepsis, diagnosis of sepsis requires the recognition of the systemic inflammatory response syndrome (SIRS) caused by infection as well as recognition of possible infection-related organ dysfunctions for diagnosis of severe sepsis or septic shock. Both SIRS and organ dysfunctions may occur frequently in hospitalized patients for various reasons. However, the fast recognition of acute infection as a cause of SIRS and newly developed organ dysfunction may be a demanding task since culture-based results of microbiological samples will be available only days after onset of symptoms. Biomarkers and PCR-based pathogen detection may help the physician in differentiating SIRS from sepsis. Procalcitonin (PCT) is the best investigated biomarker for this purpose. Furthermore, the current data support the usage of PCT for guidance of antimicrobial therapy. C-reactive protein (CRP) may be used to monitor the course of infection but has only limited discriminative capabilities. Interleukin-6 is widely used for its fast response to the infectious stimulus, but conclusive data for the application of this biomarker are missing. None of the available biomarkers can by itself reliably differentiate SIRS from sepsis but can aid and shorten the decision process. PCR-based pathogen detection can theoretically shorten the recognition of the underlying pathogen to about 8 h. However, this technique is expensive and requires additional staff in the laboratory; controlled prospective studies are missing. Although current studies suggest that PCR-based pathogen detection may be useful to shorten time to adequate antimicrobial therapy and diagnose invasive Candida infections, no general recommendations about the application of PCR for the diagnosis of sepsis can be given.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Gram-Positive Bacterial Infections; Humans; Immunoassay; Interleukin-6; Male; Middle Aged; Molecular Diagnostic Techniques; Polymerase Chain Reaction; Protein Precursors; Severity of Illness Index; Shock, Septic

We recently derived and validated a multi-biomarker-based model (ASSIST) to stratify patients with sepsis based on initial mortality risk.. The objective of this study was to compare the performance of ASSIST to interleukin-6 (IL6) and procalcitonin (PCT).. The area-under-the-receiver operating characteristic curve for predicting 28-d mortality using ASSIST was compared with that of IL6 (n = 452) and PCT (n = 235).. The area under the curve for ASSIST was greater than that of IL6 and PCT.. ASSIST estimated the probability of mortality more reliably than IL6 and PCT in this cohort of patients with sepsis.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Interleukin-6; Male; Middle Aged; Prognosis; Protein Precursors; Reproducibility of Results; Risk Assessment; Risk Factors; ROC Curve; Sepsis; Severity of Illness Index; Shock, Septic; Survival Analysis; Survival Rate

Because procalcitonin (PCT) might be surrogate for antimicrobial discontinuation in general intensive care units (ICUs), this study explored its use for secondary peritonitis in 4 surgical ICUs (SICUs).. A retrospective study including all consecutive patients with secondary peritonitis, controlled infection source, requiring surgery, and at least 48-hour SICU admission was performed (June 2012-June 2013). Patients were divided following notations in medical records into PCT-guided (notation of PCT-based antibiotic discontinuation) and non-PCT-guided (no notation) groups.. A total of 121 patients (52 PCT-guided, 69 non-PCT-guided) were included. No differences in clinical scores, biomarkers, or septic shock (30 [57.7%] PCT-guided vs 40 [58.0%] non-PCT-guided) were found. Length of intra-SICU (median, 5.0 days; both groups) or in-hospital (median, 20.0 vs 17.5 days) stay, and mortality intra-SICU (9.6% vs 13.0%), 28-day (15.4% vs 20.3%), or in-hospital (19.2% vs 29.0%) were not significantly different (PCT-guided vs non-PCT-guided). In septic shock patients, no mortality differences were found (PCT-guided vs non-PCT-guided): 16.7% vs 22.5% (intra-SICU), 26.7% vs 32.5% (28-day), and 33.3% vs 42.5% (in-hospital). Treatment was shorter in the PCT-guided group (5.1 ±2.1 vs 10.2 ± 3.7 days, P < .001), without differences between patients with and without septic shock.. Procalcitonin guidance produced 50% reduction in antibiotic duration (P < .001, log-rank test).

Topics: Aged; Aged, 80 and over; Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Hospitals; Humans; Intensive Care Units; Male; Middle Aged; Peritonitis; Protein Precursors; Retrospective Studies; Shock, Septic

To investigate the relationship between serum procalcitonin (PCT) levels and prognosis in children with bacterial meningitis.. Eighty-two child patients were included in this prospective study. The diagnosis of meningitis was based on clinical features and cerebrospinal fluid findings. PCT levels were measured with a specific immunoluminometric assay.. (a) Patients with bacterial meningitis had significantly higher serum PCT than those with viral meningitis. (b) The PCT levels of patients with severe sepsis or septic shock were significantly higher than those who had no or mild sepsis. (c) PCT levels decreased significantly in patients who had good curative effect, whereas PCT levels did not changed in patients who had no curative effect. (d) The PCT levels were significantly higher in those who died than those who survived.. Serum PCT is related to the severity of disease in children with bacterial meningitis. A fall in PCT after treatment may have favorable prognostic significance.

Topics: Adolescent; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Leukocyte Count; Male; Meningitis, Bacterial; Meningitis, Viral; Prognosis; Prospective Studies; Protein Precursors; Severity of Illness Index; Shock, Septic

The aim of this study was to determine the relationship between the time to antibiotic administration and patients' outcomes of febrile neutropenia (FN). We also investigated the relationship between the time to antibiotics and mortality rates in a subgroup of patients with bacteremia or severe sepsis or septic shock.. From the Neutropenic Fever Registry, we analyzed 1001 consecutive FN episodes diagnosed from November 1, 2011, to August 31, 2014. Timing cutoffs for antibiotics included the following: ≤1 vs. >1 h, ≤2 vs. >2 h, ≤3 vs. >3 h, and ≤4 vs. >4 h. Multivariate logistic regression was used to adjust for potential confounders in the association between timing intervals and outcomes of FN episodes.. The median length of time from triage to antibiotics was 140 min (interquartile range, 110-180 min). At each time cutoff, the time from triage to antibiotic administration was not significantly associated with FN outcomes after adjusting for potential confounders. Antibiotic timing was not significantly associated with complication rates in overall FN episodes. We failed to find a significant relationship between antibiotic timing and mortality in FN episodes with severe sepsis or septic shock or with bacteremia. Procalcitonin concentration and the Multinational Association for Supportive Care in Cancer (MASCC) risk index score were found to be more crucial determinants of outcomes in patients with FN.. The time to antibiotic administration is not a major factor in FN outcomes.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Calcitonin; Calcitonin Gene-Related Peptide; Chemotherapy-Induced Febrile Neutropenia; Female; Humans; Logistic Models; Male; Middle Aged; Neoplasms; Protein Precursors; Shock, Septic; Time-to-Treatment; Treatment Outcome; Triage

To observe the changes in plasma interleukin-33 (IL-33) in patients with sepsis and its regularity, the association between IL-33 and the infection, and the significance of IL-33 in predicting the prognosis of sepsis.. A prospective single-center single-blind clinical study was conducted. Forty patients with sepsis in intensive care unit (ICU) of Shengjing Hospital of China Medical University from May 2012 to January 2013 were enrolled. The patients were divided into general sepsis, severe sepsis and septic shock groups according to the severity of systemic infection and presence of organ dysfunction. The sepsis patients were again divided into 28-day death group and survival group. Ten healthy volunteers and 11 patients with systemic inflammatory response syndrome (SIRS) were enrolled as healthy control and SIRS groups. The levels of procalcitonin (PCT), IL-33, IL-6, IL-1β, tumor necrosis factor-α (TNF-α), and IL-33 receptor sST2 were determined with enzyme linked immunosorbent assay (ELISA) within 3 hours, and 24 hours and 5 days after enrollment to ICU. The acute physiology and chronic health evaluation II (APACHE II) score was calculated. The clinical outcome, length of stay in ICU, and duration of mechanical ventilation were recorded. The relationship between IL-33 and each parameter was analyzed by Spearman analysis. Receiver operating characteristic (ROC) curve was drawn to evaluate IL-33 in predicting the outcome of sepsis.. Plasma IL-33 in sepsis patients within 3 hours after admission was significantly increased compared with that of the healthy controls and SIRS group (ng/L: 15.43±7.22 vs. 0.67±0.24, 1.25±1.09, both P < 0.01). Compared with SIRS group, PCT in sepsis group was significantly increased [μg/L: 52.23 (19.69, 73.37) vs. 1.22 (0.69, 3.73), Z = -2.447, P < 0.001]. With exacerbation of illness, APACHE II score, the values of PCT and IL-33 were gradually increased in general sepsis, severe sepsis and septic shock groups, while the length of stay in ICU and the duration of mechanical ventilation were gradually prolonged (P < 0.05 or P < 0.01). The concentration of IL-33 (ng/L) of sepsis patients admitted to ICU within 3 hours, and 24 hours and 5 days of the illness was 15.43±7.22, 11.82±6.16, 5.55±2.25, respectively (F = 4.823, P = 0.004). There was a positive correction between IL-33 within 3 hours after ICU admission and APACHE II score (r = 0.351, P = 0.031), PCT (r = 0.412, P = 0.005), IL-6 (r = 0.535, P = 0.030), IL-1β (r = 0.674, P = 0.030), TNF-α (r = 0.250, P = 0.030), sST2 (r = 0.620, P < 0.001), and length of stay in ICU (r = 0.296, P = 0.013), duration of mechanical ventilation (r = 0.385, P = 0.011). Decreased plasma IL-33 level could be found in the survivors (n = 37, F = 7.798, P < 0.01), and its level in non-survivors (n = 3) was increased (F = 37.283, P > 0.05). The area under the ROC curve (AUC) of IL-33 and PCT in ROC curve were 0.821, 0.829. When the cut-off value of IL-33 was 13.79 ng/L, the sensitivity was 74.2%, the specificity was 79.6%; when the cut-off value of PCT was 4.70 μg/L, the sensitivity was 87.5%, and the specificity was 81.4%.. The concentration of IL-33 3 hours after ICU admission was obviously increased in sepsis patients, and it was positively correlated with PCT, therefore it is valuable in the diagnosis of the infection. In addition plasma IL-33 is related to the severity of sepsis. Its trend of change is valuable in predicting the outcome and in distinguishing sepsis from SIRS.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; China; Humans; Intensive Care Units; Interleukin-1beta; Interleukin-33; Interleukin-6; Prognosis; Prospective Studies; Protein Precursors; Respiration, Artificial; ROC Curve; Sensitivity and Specificity; Sepsis; Shock, Septic; Single-Blind Method; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

To discuss the differences of inflammatory parameters such as procalcitonin (PCT), C-reactive protein (CRP), endotoxin, white blood cell (WBC), neutrophil ratio (Neut%) in blood of septic patients caused by bacterial bloodstream infection, and their correlation with the severity of disease.. 292 septic patients with positive blood culture were enrolled in Beijing Shijitan Hospital Affiliated to Capital Medical University from February 2012 to March 2015, and their gender, age, acute physiology and chronic health evaluation II (APACHEII) score, bacterial species and other general information were retrospectively collected. The differences in inflammatory parameters (PCT, CRP, endotoxin, WBC, Neut%) in septic patients caused by bacterial bloodstream infection were compared, their correlations with APACHEII scores within 24 hours were analyzed, and their diagnostic efficacies were also analyzed.. (1) It was shown by Pearson correlation coefficients that positively statistical correlation was found between PCT (r=0.638), CRP (r=0.620), endotoxin (r=0.284), WBC (r=0.209) and APACHE II score (all P=0.000) in bacterial bloodstream infective patients (n=292), and positively statistical correlation was found between PCT (r=0.626), CRP (r=0.616), Neut% (r=0.297) and APACHE II score (all P<0.01 ) in Gram positive bacterial (G+) group (n=86), and positively statistical correlation was shown between PCT (r=0.631), CRP (r=0.616), endotoxin (r=0.301), WBC (r=0.226 ) and APACHE II score (all P<0.01) in Gram negative bacterial (G-) group (n=206). (2) It was shown that PCT and CRP of both G+/G- bacterial severe sepsis and septic shock subgroup were significantly higher than those of sepsis subgroup, respectively [G+ group: PCT (μg/L):0.92 (0.38, 4.75) vs. 0.43 (0.22, 1.00), CRP (mg/L): 118.45±62.60 vs. 57.97±32.41; G- group: PCT (μg/L):6.92 (1.94, 25.90) vs. 1.28 (0.27, 4.12), CRP (mg/L): 130.99±60.18 vs. 49.18±26.87, all P<0.01], and the endotoxin and WBC in G- bacterial severe sepsis and septic shock subgroup were significantly higher than those of sepsis subgroup [endotoxin (ng/L): 19.40 (9.62, 33.87) vs. 10.00 (5.00, 18.52), WBC (×10(9)/L): 12.13±6.72 vs. 9.61±5.01, both P<0.01]. The PCT and endotoxin in G- bacterial severe sepsis and septic shock subgroup were significantly higher than those in G+ severe sepsis and septic shock subgroup [PCT (μg/L): 6.92 (1.94, 25.90) vs. 0.92 (0.38, 4.75), endotoxin (ng/L): 19.40 (9.62, 33.87) vs. 2.56 (1.11, 4.01), both P<0.01]. (3) The diagnostic efficacy of inflammatory parameters for severe sepsis and septic shock subgroup were: PCT area under receiver operating characteristic (ROC) curve (AUC)=0.683, the cut-off point=0.55 μg/L, sensitivity 63.2%, specificity 69.0%; CRP AUC=0.802, the cut-off point=92.25 mg/L, sensitivity 73.7%, specificity 86.2%; WBC AUC=0.614, the cut-off point=7.35×10(9)/L, sensitivity 75.4%, specificity 48.3%; Neut% AUC=0.622, the cut-off point=0.882, sensitivity 43.9%, specificity 79.3% in G+ group. At the same time, it was shown that PCT AUC=0.780, the cut-off point=6.80 μg/L, sensitivity 51.0%, specificity 93.9%; CRP AUC=0.907, the cut-off point=90.10 mg/L, sensitivity 73.2%, specificity 95.9%; endotoxin AUC=0.694, the cut-off point=17.54 ng/L, sensitivity 57.3%, specificity 75.5%; WBC AUC=0.611, the cut-off point=10.54×10(9)/L, sensitivity 54.1%, specificity 69.4%; Neut% AUC=0.621, the cut-off. The plasma PCT and CRP have the best correlation between inflammatory parameters and severity of disease in bloodstream infective sepsis patients. CRP has the best diagnostic effect in severe sepsis/septic shock patients with bloodstream infection.

Topics: APACHE; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Humans; Leukocyte Count; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Shock, Septic

The case of a 74-year-old woman who presented with hyperthermia and hypotension is reported. Laboratory test results revealed marked elevation of C-reactive protein (CRP) and procalcitonin (PCT) levels. The clinical presentation and laboratory test results were suggestive of septic shock. No infectious focus was identified. The shock recurred after what was subsequently understood to be an unintended re-challenge with risedronate sodium. Drug-induced anaphylactic shock was finally diagnosed. Anaphylactic shock may be misdiagnosed as septic shock in patients who present with markedly elevated PCT levels.

Topics: Aged; Anaphylaxis; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnostic Errors; Female; Fever; Humans; Protein Precursors; Shock, Septic

To examine the effect of endotoxemia on the procalcitonin (PCT) serum levels and mortality rates of adult patients with septic shock diagnosed on the day of admission to the intensive care unit (ICU).A retrospective observational study was performed over a 2-year period. Levels of PCT were compared for septic shock patients with and without endotoxemia on admission to the ICU. Endotoxemia was identified with an Endotoxin Activity Assay.One hundred fifty-seven patients with septic shock were enrolled into the study. Group 1 consisted of patients with elevated endotoxin activity (EA) (n = 95, EA = 0.57 endotoxin activity unit [EAU] [0.46-0.67]) and Group 2 consisted of patients with low EA (n = 62, EA = 0.27 EAU [0.17-0.36]). Acute Physiology And Chronic Health Evaluation II (APACHE II) score and SOFA score were similar in both groups (APACHE II = 23 [16-29] and 19 [16-25]; Sequential Organ Failure Assessment [SOFA] = 10 [7-13] and 11 [8-12] in Groups 1 and 2, respectively) (nonsignificant). The PCT level was 6 times higher in Group 1 than in Group 2 (19.6 ng/mL vs. 3.1 ng/mL, P < 0.001). There was a strong correlation between EA and serum PCT (P < 0.001, R = 0.5). The presence of endotoxemia on admission to the ICU was associated with an increased mortality rate: 52% in the group of patients with endotoxemia and 25% in the group without endotoxemia. EA in survivors was 0.39 EAU (0.26-0.57) and 0.53 EAU (0.4-0.61) in nonsurvivors (P = 0.004). The median PCT level in survivors was 6.7 ng/mL (2.3-28.0), compared with 16.7 ng/mL (5.3-31.0) in nonsurvivors (P = 0.04).This observational study revealed that endotoxemia in patients with septic shock on admission to the ICU was frequently found and was associated with an elevated PCT level and a high mortality rate. Endotoxemia was a common occurrence in patients with septic shock, regardless of the infecting microorganism.

Topics: Aged; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxemia; Female; Humans; Intensive Care Units; Kaplan-Meier Estimate; Male; Middle Aged; Organ Dysfunction Scores; Protein Precursors; Retrospective Studies; Shock, Septic

Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF.. Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls.. Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups-non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169). PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001)). Subjects with acetaminophen (APAP) toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL.. While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Inflammation; Liver Failure, Acute; Male; Middle Aged; Prospective Studies; Protein Precursors; Retrospective Studies; Sepsis; Severity of Illness Index; Shock, Septic; Systemic Inflammatory Response Syndrome; Young Adult

To explore the early diagnostic value of pro-adrenomedullin (pro-ADM) in sepsis.. A prospective study was conducted. Eighty-two patients with acute infection admitted to Department of Emergency of Shanxi Medical University Second Hospital from April 2013 to March 2014 were enrolled. According to the diagnostic criteria of sepsis, the patients with acute infection were divided into ordinary infection group [infection without systemic inflammatory response syndrome (SIRS), n = 25] and sepsis group (infection combined with SIRS, n = 57). According to degree of severity of sepsis, the latter group was subdivided into three subgroups: sepsis group (n = 22), severe sepsis group (n = 27) and septic shock group (n = 8). Twenty-four healthy persons were included to serve as healthy control group. The venous blood from all the research objects in hospital was collected within 24 hours. The levels of pro-ADM and procalcitonin ( PCT ) were determined by enzyme linked immunosorbent assay (ELISA), and acute physiology and chronic health evaluation II (APACHE II ) score was recorded. The relationship between pro-ADM and PCT and also APACHE II score was analyzed with Pearson correlation analysis. The receiver-operating characteristic curve (ROC) of pro-ADM and PCT were used to evaluate the diagnostic acuity of sepsis.. The plasma levels of pro-ADM, PCT and APACHE II score in sepsis group were significantly higher than those in ordinary infection group and healthy control group [pro-ADM (ng/L): 66.69 ± 1.73 vs. 53.43 ± 2.70, 45.87 ± 1.43; PCT (ng/L): 1 336.49 ± 40.26 vs. 1 083.09 ± 47.99, 959.04 ± 37.53; APACHE II score: 14.60 ± 0.81 vs. 8.10 ± 1.14, 3.00 ± 1.15, all P < 0.01]. With the aggravation of sepsis, the levels of pro-ADM, PCT and APACHE II score were gradually increased, and there were significant differences among sepsis, severe sepsis, and septic shock groups [pro-ADM (ng/L): 64.91 ± 2.50, 73.56 ± 2.80, 84.67 ± 4.52; PCT (ng/L): 1 152.65 ± 48.62, 1 233.93 ± 63.06, 1 475.71 ± 109.93; APACHE II score: 12.91 ± 1.15, 14.55 ± 1.14, 19.37 ± 2.40, P < 0.05 or P < 0.01]. Pearson correlation analysis results showed that the level of pro-ADM was positively related with PCT (r = 0.473, P = 0.006), and it was also positively correlated with APACHE II score (r = 0.707, P = 0.008). ROC curve analysis showed that area under the ROC curve (AUC) of pro-ADM for diagnosis of sepsis was 0.823 (P = 0.003). When the cutoff value was 59.40 ng/L, the sensitivity was 80.7%, the specificity was 68.0%, the positive predictive value was 85.2%, and the negative predictive value was 60.7%. AUC of the PCT for diagnosis of sepsis was 0.653 (P = 0.043). When the cutoff value was 1 194.67 ng/L, the sensitivity was 68.4%, the specificity was 64.0%, the positive predictive value was 81.8%, and the negative predictive value was 44.7%. It was proved that the pro-ADM had a higher diagnostic value for sepsis than PCT.. The plasma levels of pro-ADM can be used as an early indicator in diagnosis and severity evaluation and prognosis in patients with sepsis.

Topics: Adrenomedullin; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Humans; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Kynurenic acid (KYNA) is one of the end products of tryptophan metabolism. The aim of this study was to analyse plasma KYNA concentration in septic shock patients (SSP) with acute kidney injury (AKI) undergoing continuous veno-venous haemofiltration (CVVH). Changes in KYNA content were compared to alterations in the levels of procalcitonin (PCT), C-reactive protein and lactate. Adult SSP with AKI were examined. Measurements were conducted at seven time points: before beginning CVVH and at 6, 12, 24, 48, 72 and 96 h after the beginning of CVVH. Based on clinical outcomes, the data were analysed separately for survivors and non-survivors. Twenty-seven patients were studied. CVVH was associated with reduced plasma KYNA concentration only in survivors. Plasma KYNA concentration correlated with the levels of lactate and PCT only in survivors. (1) CVVH reduced plasma KYNA concentration only in survivors; (2) lack of this reduction may predict fatal outcomes in SSP.

Topics: Acute Kidney Injury; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hemofiltration; Humans; Kynurenic Acid; Lactic Acid; Male; Middle Aged; Multiple Organ Failure; Mycoses; Protein Precursors; Pyometra; Shock, Septic; Treatment Outcome; Urinary Tract Infections

To determine the usefulness of procalcitonin (PCT) in decision-making when faced with suspected infection in patients with extensive burns.. Retrospective, observational follow-up study.. Burn Unit of the Complexo Hospitalario Universitario A Coruña (CHUAC), Spain.. We included all patients admitted to the Unit from June 2011 to March 2012 with ≥20% total body surface area burned or ≥10% full-thickness body surface area burned with suspected infection (17 patients with 34 events of suspected infection).. The infections were confirmed in 16/34 episodes (47.1%), and documented in 44.1% (n=15). There were no statistically significant differences in the PCT figures at the time the infection was suspected between the cases with confirmed and unconfirmed infection (p=0.682). The PCT values showed no discriminative value for differentiating patients with SIRS from those with sepsis, severe sepsis and septic shock (area under ROC curve (AUC)=0.546; 95% CI: 0.326-0.766). No significant correlation was found between SOFA and PCT, although there were differences in the PCT values in the patients who had tissue hypoperfusion.. Results show that PCT is not a precise indicator of sepsis at the time of diagnosis. A correlation between PCT levels and hypoperfusion was observed.

Topics: Adult; Aged; Area Under Curve; Biomarkers; Burn Units; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Shock, Septic; Smoke Inhalation Injury; Systemic Inflammatory Response Syndrome; Young Adult

The aim of our study is to test procalcitonin (PCT) as surrogate marker of identification of Candida spp. by blood culture (BC) and real-time-polymerase chain reaction (PCR), whether alone or in association with bacteria, in septic patients.. We performed a single-centre retrospective study. We reviewed the clinical charts of patients with a diagnosis of severe sepsis or septic shock treated at our general intensive care unit from March 2009 to March 2013. We analysed all diagnostic episodes consisting of BC, real-time PCR assay and dosage of PCT. We registered age, sex, white blood count, sequential organ failure assessment score and type of admission between medical or surgical. When inclusion criteria were met more than once, we registered the new diagnostic episode as subsequent diagnostic episode. The diagnostic performance of PCT to predict Candida spp. identification alone or in mixed infections by either BC or PCR was tested using the receiver-operative characteristic curve. Logistic regression was constructed using presence of Candida spp. as the dependent variable.. A total of 260 diagnostic episodes met the inclusion criteria. According to BC results classification, a significantly lower value of PCT was observed in Candida spp. BSI (0.99 ng/ml, 0.86 - 1.34) than in BSI caused by bacteria (16.7 ng/ml, 7.65 - 50.2) or in mixed infections (4.76 ng/ml, 2.98 - 6.08). Similar findings were observed considering PCR results. A cut-off of ≤ 6.08 ng/ml for PCT yielded a sensitivity of 86.8%, a specificity of 87.4%, a positive predictive value of 63.9%, a negative predictive value (NPV) of 96.3% and an area under the curve of 0.93 for Candida spp. identification by BC. A similar high NPV for a cut-off ≤ 6.78 ng/ml was observed considering the classification of diagnostic episodes according to PCR results, with an AUC of 0.85. A subsequent diagnostic episode was independently associated with Candida spp. detection either by BC or PCR.. PCT could represent a useful diagnostic tool to exclude the detection of Candida spp. by BC and PCR in septic patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Candida; Female; Humans; Male; Middle Aged; Protein Precursors; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sepsis; Shock, Septic

To understand how coupled plasma filtration and adsorption (CPFA) could influence the time course of the advanced stages of sepsis, mean arterial pressure (MAP) and norepinephrine dosage.. Patients with severe sepsis and septic shock with ≥2 organ failures not responding to volume resuscitation and vasopressor infusion were treated with CPFA within 8 h of admission to the intensive care unit.. Thirty-nine patients were treated (median age: 63 years, median SAPS II score: 45) and 28 survived advanced sepsis. In the latter, the median MAP increased and the norepinephrine dosage decreased significantly after CPFA, whereas in the nonsurvivors these values did not change significantly. The volume of treated plasma was significantly higher in survivors than nonsurvivors.. These results suggest a possible existence of a dose-response effect for CPFA. Future studies are therefore recommended to evaluate the efficacy of this treatment and to determine its best timing and intensity.

Topics: Aged; Arterial Pressure; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hemodynamics; Hemofiltration; Humans; Intensive Care Units; Male; Middle Aged; Protein Precursors; Sepsis; Shock, Septic; Treatment Outcome

The purpose of this study is to investigate the effect of serial lysophosphatidylcholine (LPC) measurement on 28-day mortality prediction in patients with severe sepsis or septic shock admitted to the medical intensive care unit (ICU).. This is a prospective observational study of 74 ICU patients in a tertiary hospital. Serum LPC, white blood cell, C-reactive protein, and procalcitonin (PCT) levels were measured at baseline (day 1 of enrollment) and day 7. The LPC concentrations were compared with inflammatory markers using their absolute levels and relative changes.. The LPC concentration on day 7 was significantly lower in nonsurvivors than in survivors (68.45 ± 42.36 μmol/L and 99.76 ± 73.65 μmol/L; P = .04). A decreased LPC concentration on day 7 to its baseline as well as a sustained high concentration of PCT on day 7 at more than 50% of its baseline value was useful for predicting the 28-day mortality. Prognostic utility was substantially improved when combined LPC and PCT criteria were applied to 28-day mortality outcome predictions. Furthermore, LPC concentrations increased over time in patients with appropriate antibiotics but not in those with inappropriate antibiotics.. Serial measurements of LPC help in the prediction of 28-day mortality in ICU patients with severe sepsis or septic shock.

Topics: Aged; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospitalization; Humans; Intensive Care Units; Lymphocyte Count; Lysophosphatidylcholines; Male; Middle Aged; Organ Dysfunction Scores; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic; Time Factors

A 62-year-old man was scheduled for transurethral lithotripsy. Systemic shivering, vomiting and decreased blood pressure occurred after extubation. Blood gas analysis showed metabolic acidosis. After 45 minute observation, he became unconsciousness. He was reintubated. Elevated procalcitonin (PCT) and endotoxin activity assay (EAA) brought us to the diagnosis of severe septic shock. He was treated by a standard therapy conforming to early goal direct therapy and PMX-DHP with CHDF. He showed full recovery, and was discharged 9 days after the procedure. TUL is commonly performed, but it seldom leads to sepsis. We need to pay a careful attention peri- and postoperatively.

Topics: Anesthesia, General; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Hemodiafiltration; Hemoperfusion; Humans; Infusions, Intravenous; Kidney Calculi; Lithotripsy; Male; Meropenem; Middle Aged; Protein Precursors; Severity of Illness Index; Shock, Septic; Thienamycins; Treatment Outcome; Urethra

Although a few prospective studies have addressed the question as to which biomarker of infection in adult patients with febrile neutropenia (FN) is superior, procalcitonin (PCT) or C-reactive protein (CRP), the results have been inconsistent and inconclusive. This was possibly due to the poor sensitivity of previous PCT tests that have a functional sensitivity of 0.5 ng/ml.. Between November 2010 and February 2012, we prospectively compared the diagnostic utility of serum high-sensitivity (hs) PCT (lower limit of detection, 0.02 ng/ml) and CRP levels for detecting bacterial infection in patients with FN. Serum was collected within 72 h after the onset of FN in patients with hematological disorders.. Seventy-five febrile episodes were evaluable. The areas under the receiver operating characteristic curves for life-threatening infection defined as septic shock and bacteremia caused by non-coagulase negative staphylococcus were 0.824 (95% CI 0.711-0.937; P = 0.001) for hsPCT and 0.673 (0.505-0.842; P = 0.068) for CRP, respectively. In contrast, CRP, but not hsPCT, tended to increase significantly with the clinical severity, as indicated by the diagnostic classification (P = 0.002 for trend).. The serum hsPCT test may be more useful than the serum CRP test in the detection of life-threatening infection at an early phase after the onset of FN. In contrast, the serum CRP test may be more useful in diagnosing the severity of infection. However, neither of these tests was able to differentiate the cause of FN with a low probability of fatal outcome.

Topics: Adolescent; Adult; Aged; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Febrile Neutropenia; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; ROC Curve; Shock, Septic; Young Adult

This study was to investigate the diagnostic value of serum procalcitonin(PCT) in identifying the etiology of non-responding community-acquired pneumonia (CAP) after initial antibiotic therapy.. A retrospective analysis was performed for 232 hospitalized CAP patients admitted to the People's Hospital of Zhengzhou University during June 2013 and January 2014. Early treatment failure was defined as the presence of persistent fever (>38 °C) and/or clinical symptoms (malaise, cough, expectoration, dyspnea) or deterioration after at least 72 h of initial antimicrobial treatment, or development of respiratory failure requiring mechanical ventilation, or septic shock. Bronchoscopy or transthoracic lung biopsy was performed in case of early treatment failure when indicated. Serum level of PCT was detected by double antibody sandwich method. The differences between 2 or more groups were compared using 2-independent student t test, one-way ANOVA; Mann-Whitney U test, Kruskal-Wallis rank sum test, or χ(2) test. Risk factors and odds ratios for nonresponsiveness were analyzed by setting up a Logistic regression model. The diagnostic values of PCT were determined by receiver operating characteristic curves (ROC curves).. Of the 232 CAP patients enrolled, 124 were male and 108 were female, with an average age of (46 ± 20) years. Thirty-six patients failed to respond to the initial antibiotic therapy. As shown by Logistic regression analysis, the risk factors for treatment failure included hypoalbuminemia, type 2 diabetes, previous history of splenectomy , PSI 4-5 grade, and lung infiltration ≥ 3 lobes. The most common causes of non-responsiveness were antimicrobial insufficiency (n = 23), and misdiagnosis of noninfectious mimics of pneumonia (n = 11), with 2 cases of unidentified etiology. The serum PCT level in admission was 0.19 (0.07-0.66) µg/L in the antimicrobial insufficiency subgroup, which was significantly higher than that in the misdiagnosis subgroup [0.06(0.05-0.08)µg/L; P < 0.01]. The antimicrobial insufficiency subgroup included 11 cases of bacterial infection (5 of G(+) cocci and 6 of G(-) bacilli) and 12 cases of nonbacterial infection; their PCT levels were 0.66(0.19-5.80) µg/L and 0.08(0.05-0.20) µg/L, respectively (P < 0.01). There was no statistically significant difference among PCT levels of the 4 subgroups of nonbacterial infections (4 tuberculosis, 3 fungi, 3 atypical pathogens, 2 viruses) (F = 3.025, P = 0.094). The cut-off values of PCT were >0.13 µg/L and >0.115 µg/L for differentiating non-responsiveness originated from bacterial infection or other causes, and infection vs non-infection, which yielded a sensitivity of 100% (11/11) and 65% (14/23) , specificity of 83% (19/23) and 91% (10/11) , and AUC of 0.955 and 0.802, respectively.. Antibiotic failure to cover the microbial pathogens, infectious complications and misdiagnosis are the most common causes of early treatment failure in patients with CAP. Serum PCT level fails to predict non-responsiveness, but is suggestive of bacterial infections in hospitalized CAP patients with early treatment failure.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Male; Middle Aged; Pneumonia; Prognosis; Protein Precursors; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Shock, Septic; Statistics, Nonparametric

Immediate initiation of hemoperfusion treatment with polymixin B immobilized fiber (PMX-DHP) is a potent strategy to improve hemodynamics in septic patients with critical circulatory failure. However, it is often difficult to accurately and rapidly differentiate between bacterial infections and non-infectious causes of shock in acutely critically-ill patients. Procalcitonin (PCT) measurements may assist in the early identification of bacterial infection/sepsis and determination of severity in such patients. We present two febrile neutropenic (FN) patients who developed severe shock after chemotherapy for hematological malignancies. PCT levels were markedly elevated in both patients (≥ 10 ng/ml), suggesting a high likelihood of bacterial infectious etiology as the cause of their shock, and thus they were promptly treated with PMX-DHP. Measurements of PCT may facilitate targeting of PMX-DHP treatment among FN patients suffering from shock, which may lead to better prognosis.

Topics: Adsorption; Adult; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Febrile Neutropenia; Female; Hemoperfusion; Humans; Male; Polymyxin B; Protein Precursors; Shock, Septic

Procalcitonin (PCT) is an early, sensitive, and accurate marker for diagnosing infection and sepsis. As sepsis and septic shock are dominant causes of acute kidney injury (AKI), we investigated whether PCT is an early predictor of AKI in patients with symptoms of infection.. Between January 2011 and October 2011, 1361 inpatients in West China Hospital who displayed infection symptoms were enrolled in our study. Levels of PCT, serum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cell count (WBC) were determined and participants' renal function was monitored for 3 consecutive days.. The rate of AKI occurrence 3 days after enrollment was 14.6%. Higher PCT levels were correlated with higher AKI occurrence rates and higher levels of serum urea, creatinine, and cystatin C (p<0.05). The area under the receiver-operating characteristic (ROC) curve (AUC) for PCT was 0.823, making it more predictive (p<0.0001) than SAA, CRP, IL-6, or WBC. The cut-off value of 1.575 ng/mL for PCT had the highest validity for predicting AKI in patients with infection symptoms. The sensitivity, specificity, negative-predictive value (NPV), positive-predictive value (PPV), negative-likelihood ratio (LR-), and positive-likelihood ratio (LR+) for this cut-off value were 61.7%, 84.6%, 93.6%, 37.5%, 0.415, and 4.98, respectively.. PCT can be used as a predictive marker for sepsis-induced acute kidney injury in patients with symptoms of infection.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; Sensitivity and Specificity; Sepsis; Shock, Septic; Young Adult

Previous studies have shown that cysteine-rich secretory protein containing LCCL domain 2 (CRISPLD2) is a novel lipopolysaccharide (LPS)-binding protein, and the upregulation of CRISPLD2 expression protects mice against LPS-induced lethality. The aim of this study was to examine the expression of CRISPLD2 in patients with sepsis and characterize the association of this protein with procalcitonin.. The expression of CRISPLD2 was determined in 100 healthy volunteers and 119 septic patients. According to the definition of sepsis, patients were divided into three groups sepsis, severe sepsis, and septic shock. The relationship between CRISPLD2 levels and procalcitonin was also examined and statistically analyzed.. The CRISPLD2 levels in healthy individuals were 219.3±69.1 µg/ml. Patients with sepsis exhibited higher CRISPLD2 levels than observed in healthy individuals (p = 0.001), but CRISPLD2 expression was not upregulated in patients with septic shock. No significant differences were observed between the levels of CRISPLD2 in surviving and non-surviving spesis patients. CRISPLD2 levels were negatively correlated with procalcitonin levels (r = -0.334, p<0.001).. The present study is the first to demonstrate the decreased expression of CRISPLD2 in septic shock and its association with PCT in sepsis. Further studies are needed to clarify the potential association between CRISPLD2 expression and clinical outcomes to determine if it could be used as a novel sepsis biomarker.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Cell Adhesion Molecules; Female; Gene Expression; Humans; Interferon Regulatory Factors; Male; Middle Aged; Protein Precursors; Sepsis; Shock, Septic; Treatment Outcome

To investigate procalcitonin (PCT) change pattern in patients with septic shock and its relationship with prognosis.. Sixty-three septic shock patients were enrolled, and levels of PCT, C-reactive protein (CRP) as well as white blood cell (WBC) on 1st, 3rd, 5th,7th day after admission to intensive care unit (ICU) were checked. Patients were divided into survival group and death group according to 28-day survival result. Differences in parameters between two groups were compared. The change regulation of parameters along with in-hospital period and its relationship with prognosis were analyzed by multilevel linear model.. There were 41 patients in survival group and 22 patients in death group. PCT and CRP level decreased in survival group with time dependency pattern, while death group increased. The PCT at 3, 5, 7 days after admission to ICU in death group were significantly higher than those in survivors (3 days: 8.7±3.7 μg/L vs. 5.6±1.7 μg/L, 5 days: 10.3±1.3 μg/L vs. 4.8±2.3 μg/L, 7 days: 12.7±2.3 μg/L vs. 0.8±0.3 μg/L, P<0.05 or P<0.01), and CRP at 5 days and 7 days was significantly higher than those in survival group (5 days: 447±63 mg/L vs. 355±91 mg/L, 7 days: 439±45 mg/L vs. 364±63 mg/L, both P<0.05). Two groups of WBC did not change significantly, and there were no statistical significance difference at each time point between the two groups. What's more, the effect analysis results showed that there were significant changes in PCT as ICU day prolonged (F=10.91, P= 0.00), and there was a significant difference between the survivor and the dead (F=7.58, P=0.00), while CRP changed only with ICU stays (F=4.17, P=0.03).. Compared with CRP and WBC, PCT had higher sensitivity in predicting prognosis, sustainable elevation of PCT level indicates poor prognosis, serum PCT can be used as one of indexes predicting prognosis of septic shock.

Topics: Adult; Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Prognosis; Protein Precursors; Shock, Septic; Survival Rate

Soluble thrombomodulin (sTM) is a sensitive marker of endothelial damage. In this study we investigated the role of sTM in the evaluation of the severity and prognosis of septic patients in the emergency department (ED).. A prospective, observational cohort study was performed in the ED of an urban, university hospital. Patients who had suspected infection with two or more criteria of systemic inflammatory response syndrome were consecutively enrolled. sTM, D-Dimer and procalcitonin levels were measured on enrollment, and the Mortality in Emergency Department Sepsis (MEDS) score was calculated. A 30-day follow-up was performed for all patients.. A total of 372 patients with sepsis, 210 patients with severe sepsis and 98 patients with septic shock were enrolled in this study. According to the disease severity, patients were divided into sepsis subgroup and severe sepsis subgroup (including septic shock). In addition, patients were divided into survivors subgroup and non-survivors subgroup according to the 30-day mortality. Plasma sTM levels in patients with severe sepsis were higher than those with sepsis (P<0.001). Compared with survivors, non-survivors has higher plasma sTM levels (P<0.001). Multivariate logistic regression analysis showed that sTM was an independent predictor of severe sepsis (odds ratio 1.11) and 30-day mortality (odds ratio 1.059). Receiver operating characteristic curve analysis showed that sTM was a useful parameter in prediction of severe sepsis (0.859) and 30-day mortality (0.78). Compared with the MEDS score alone, combination of sTM and the MEDS score can improve the accuracy in prediction of severe sepsis and 30-day mortality.. sTM is a valuable biomarker in the risk stratification and prognosis evaluation of ED sepsis. Furthermore, sTM can enhance the ability of the MEDS score in prediction of severe sepsis and 30-day mortality.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Emergency Service, Hospital; Female; Fibrin Fibrinogen Degradation Products; Humans; Immunohistochemistry; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Sepsis; Shock, Septic; Thrombomodulin; Triage

Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841-0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812-0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergencies; Endotoxins; Female; Gastrointestinal Tract; Humans; Lasers; Limulus Test; Male; Middle Aged; Nephelometry and Turbidimetry; Photometry; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Protein Precursors; Scattering, Radiation; Sepsis; Shock, Septic

Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis.. This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann-Whitney U tests.. On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days' follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group.. Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED.

Topics: Aged; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; China; Female; Humans; Lipopolysaccharide Receptors; Male; Middle Aged; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Shock, Septic; Systemic Inflammatory Response Syndrome

Procalcitonin (PCT) biomarker is suggested to tailor antibiotic therapy in the medical intensive care unit (ICU) but studies in perioperative medicine are scarce. The aim of this study was to determine whether PCT reported thresholds are associated with the initial treatment response in perioperative septic shock secondary to intra-abdominal infection.. This single ICU, observational study included patients with perioperative septic shocks secondary to intra-abdominal infection. Demographics, PCT at days 0, 1, 3, 5, treatment response and outcome were collected. Treatment failure included death related to the initial infection, second source control treatment or a new onset intra-abdominal infection. The primary endpoint was to assess whether PCT thresholds (0.5 ng/ml or a drop from the peak of at least 80%) predict the initial treatment response.. We included 101 consecutive cases. Initial treatment failed in 36 patients with a subsequent mortality of 75%. Upon admission, PCT was doubled when treatment ultimately failed (21.7 ng/ml ± 38.7 vs. 41.7 ng/ml ± 75.7; P = 0.04). Although 95% of the patients in whom PCT dropped down below 0.5 ng/ml responded to treatment, 50% of the patients in whom PCT remained above 0.5 ng/ml also responded successfully to treatment. Moreover, despite a PCT drop of at least 80%, 40% of patients had treatment failure.. In perioperative intra-abdominal infections with shock, PCT decrease to 0.5 ng/ml lacked sensitivity to predict treatment response and its decrease of at least 80% from its peak failed to accurately predict treatment response. Studies in perioperative severe infections are needed before using PCT to tailor antibiotic use in this population.

Topics: Aged; Anti-Infective Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intraabdominal Infections; Male; Predictive Value of Tests; Protein Precursors; Shock, Septic; Treatment Outcome

The ideal management of infection includes not only the early identification and start of effective therapy but also the correct categorization of non-infected patients in order to avoid unnecessary use of antimicrobials. The availability of a specific and sensitive test for the presence of infection is of paramount importance to improve the prudent use of antimicrobial therapy. Procalcitonin (PCT) has been evaluated over recent years as to whether it can be used to detect the presence of different types of infection, allows reduced duration of antibiotic therapy, or predicts treatment failure or adverse outcome. In the previous issue of Critical Care, Jung and colleagues report about the monitoring of treatment response in abdominal sepsis by repetitive determination of PCT.

Topics: Anti-Infective Agents; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intraabdominal Infections; Male; Protein Precursors; Shock, Septic

To evaluate procalcitonin clearance as a prognostic biomarker in septic shock.. Prospective, observational pilot study.. Intensive care unit.. Patients admitted to the ICU due to septic shock and multiorgan dysfunction.. Serum concentrations of procalcitonin were determined within 12h of onset of septic shock and multiorgan dysfunction (coinciding with admission to the ICU), and the following extractions were obtained after 24, 48 and 72h in patients who survived.. Demographic data, Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score, data on the primary focus of infection, and patient outcome (ICU mortality).. Procalcitonin clearance was higher in survivors than in non-survivors, with significant differences at 24h (73.9 [56.4-83.8]% vs 22.7 [-331-58.4], p<0.05) and 48h (81.6 [71.6-91.3]% vs -7.29 [-108.2-82.3], p<0.05). The area under the ROC curve was 0.74 (95%CI, 0.54-0.95, p<0.05) for procalcitonin clearance at 24h, and 0.86 (95%CI, 0.69-1.0, p<0.05) at 48h.. ICU mortality was associated to sustained high procalcitonin levels, suggesting that procalcitonin clearance at 48h may be a valuable prognostic biomarker.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Multiple Organ Failure; Pilot Projects; Prognosis; Prospective Studies; Protein Precursors; Shock, Septic

Patients with hematological neoplasms transferred to an Intensive Care Unit (ICU) for a life-threatening complication have a poor outcome. In these patients, it is crucial to identify clinical and biologic parameters with potential prognostic significance. This study prospectively evaluated the usefulness of serum procalcitonin (PCT) levels as a predictor of complications (infectious or not) and outcome in these patients.. One hundred patients with hematological malignancy were admitted to the ICU from October 2004 until August 2009. In 59 of them serum PCT levels were daily measured from the ICU admission until a maximum period of 10 consecutive days.. Hematological diseases were acute leukemia (n=30), lymphoma and other lymphoproliferative disorders (n=18), multiple myeloma (n=7) and other (n=4). Twenty-five patients (42%) had received hematopoietic stem cell transplantation. Thirty-seven patients (63%) presented neutropenia. Those patients who could not be discharged alive from the ICU presented higher PCT levels on days 1, 2 and 3. PCT levels were significantly higher in those patients with neutropenia or septic shock or other causes of hemodynamic instability. The presence of a microbiologically documented infection, respiratory failure or the need of mechanical ventilation support did not significantly affect PCT levels in this study.. Early serum PCT levels measurement might be useful for predicting mortality in patients with hematological malignancy requiring advanced life support.

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Combined Modality Therapy; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hemodynamics; Humans; Infections; Intensive Care Units; Lymphoproliferative Disorders; Male; Middle Aged; Neutropenia; Protein Precursors; Respiratory Insufficiency; Shock, Septic; Treatment Outcome; Young Adult

Biomarkers, such as C-reactive protein [CRP] and procalcitonin [PCT], are insufficiently sensitive or specific to stratify patients with sepsis. We investigate the prognostic value of pancreatic stone protein/regenerating protein (PSP/reg) concentration in patients with severe infections.. PSP/reg, CRP, PCT, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1-β), IL-6 and IL-8 were prospectively measured in cohort of patients ≥ 18 years of age with severe sepsis or septic shock within 24 hours of admission in a medico-surgical intensive care unit (ICU) of a community and referral university hospital, and the ability to predict in-hospital mortality was determined.. We evaluated 107 patients, 33 with severe sepsis and 74 with septic shock, with in-hospital mortality rates of 6% (2/33) and 25% (17/74), respectively. Plasma concentrations of PSP/reg (343.5 vs. 73.5 ng/ml, P < 0.001), PCT (39.3 vs. 12.0 ng/ml, P < 0.001), IL-8 (682 vs. 184 ng/ml, P < 0.001) and IL-6 (1955 vs. 544 pg/ml, P < 0.01) were significantly higher in patients with septic shock than with severe sepsis. Of note, median PSP/reg was 13.0 ng/ml (IQR: 4.8) in 20 severely burned patients without infection. The area under the ROC curve for PSP/reg (0.65 [95% CI: 0.51 to 0.80]) was higher than for CRP (0.44 [0.29 to 0.60]), PCT 0.46 [0.29 to 0.61]), IL-8 (0.61 [0.43 to 0.77]) or IL-6 (0.59 [0.44 to 0.75]) in predicting in-hospital mortality. In patients with septic shock, PSP/reg was the only biomarker associated with in-hospital mortality (P = 0.049). Risk of mortality increased continuously for each ascending quartile of PSP/reg.. Measurement of PSP/reg concentration within 24 hours of ICU admission may predict in-hospital mortality in patients with septic shock, identifying patients who may benefit most from tailored ICU management.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Health Status Indicators; Hospital Mortality; Humans; Intensive Care Units; Interleukin-1beta; Interleukin-6; Interleukin-8; Lithostathine; Male; Middle Aged; Pancreatitis; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

It has been shown that pro-adrenomedullin is a good marker of the severity of septic shock but there are no data on the early changes in serum pro-adrenomedullin concentrations in patients with shock.. Twenty-one patients with septic shock and 21 healthy subjects studied as controls. Serum concentrations of pro-adrenomedullin, procalcitonin, ferritin, CRP and IL-6 were determined in all subjects at the initial observation. Patients with septic shock were also studied after 24 and 48 hours.. The concentrations of the acute phase proteins were significantly higher in patients with septic shock than in the control subjects during the entire study period (P<0.001). Only procalcitonin significantly decreased on the third day of observation with respect to both the first day (P=0.002) and the second day (P=0.006). Proadrenomedullin (P=0.017) and IL-6 (P=0.001) showed an AUC significantly different from the null hypothesis in differentiating the patients who survived and those who did not. The sensitivity and specificity of pro-adrenomedullin in the assessment of death were 71.4% and 72.7%, respectively, while IL-6 had a sensitivity of 92.9% and a specificity of 60.6%.. Proadrenomedullin is a reliable prognostic marker in patients with shock; further studies on a more consistent number of septic patients will definitively assess whether proadrenomedullin may replace the current prognostic markers in critically ill patients with shock due to sepsis.

Topics: Acute-Phase Proteins; Adrenomedullin; Adult; Aged; Aged, 80 and over; Area Under Curve; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Ferritins; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Prognosis; Protein Precursors; Sensitivity and Specificity; Shock, Septic; Time Factors

To investigate the predictor value of peripheral blood procalcitonin (PCT) levels in the evaluation of prognosis of patients with septic shock.. A prospective study was conducted. Eighty-four patients with septic shock in intensive care unit (ICU) of Beijing Shijitan Hospital Affiliated to Capital Medical University were enrolled from May, 2011 to January, 2012. Serum PCT levels were monitored, and the acute physiology and chronic health evaluation II (APACHEII) score, sequential organ failure assessment (SOFA) score were recorded at the 1st, 3rd, 5th, and 7th day after admission. According to the 28-day outcome after admission to ICU, the patients with septic shock were divided into the survivor group and non-survivor group, dynamic changes in serum PCT levels were compared between two groups and correlation analysis was carried out on serum PCT levels and the APACHEII score, SOFA score.. (1) There was no significant difference in serum PCT levels (μg/L) at the 1st and 3rd day between survivor group (n=38) and non-survivor group (n=46), but the serum PCT levels at the 5th and 7th day in non-survivor group were significantly higher than that in survivor group (5 days: 8.79±2.38 vs. 2.38±0.88, 7 days: 12.57±3.29 vs. 0.71±0.22, both P<0.05), and the drop of PCT concentrations were significant compared with survivor group (1.91±1.21 vs. 10.27±4.49, P<0.05). At the same time, positive statistical correlation was found between serum PCT levels and APACHEII score, SOFA score (5 days: R(APACHEII)=0.395, R(SOFA)=0.396; 7 days: R(APACHEII)=0.675, R(SOFA)=0.648, all P<0.01). (2) Receiver operator characteristic curve (ROC curve) of serum PCT levels on the 7th day could significantly predict the 28-day mortality, maximal area under the curve (AUC) of PCT was 0.886. When PCT was 0.965 μg/L, the sensitivity and specificity were appropriate. By multivariate factors logistic regression, serum PCT concentrations were not significantly correlated with 28-day mortality. (3) The median survival time (days) of patients with 7-day PCT <1.0 μg/L was far more than that of the patients with PCT>1.0 μg/L (28.0 vs. 14.1, P<0.05).. Dynamic monitoring of serum PCT levels can help to assessment the prognosis of septic shock and also in predicting the severity of the illness, but it may not be a significant independent prognostic marker for 28-day survival in the patients with septic shock.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Shock, Septic; Young Adult

Early diagnosis of complicated course in febrile neutropenia is cumbersome due to the non-specificity of clinical and laboratory signs of severe infection. This prospective study included 100 adult hematological patients with febrile neutropenia after intensive chemotherapy at the onset of fever (d0) and for 3 days (d1-d3) thereafter. The study aim was to find early predictors for complicated course of febrile neutropenia, defined as bacteremia or septic shock. Interleukin 6 (IL-6), interleukin 10 (IL-10), procalcitonin (PCT) and C-reactive protein (CRP) all predicted complicated course of febrile neutropenia on d0, but only PCT was predictive throughout the study period. For IL-10 on d0-1 with cut-off 37 ng/L, sensitivity was 0.71, specificity 0.82, positive predictive value 0.52 and negative predictive value 0.92. For PCT on d0-1 with cut-off 0.13 μg/L, the respective measures were 0.95, 0.53, 0.36, and 0.98. For the combination of IL-10 and PCT on d0-1 with the same cut-offs, specificity improved to 0.85 and positive predictive value to 0.56. In conclusion, the present study confirms the high negative predictive value of PCT and provides new evidence for IL-10 as an early predictor for complicated course of febrile neutropenia in hematological patients. Combining IL-10 with PCT improves the early prediction for complicated course of febrile neutropenia.

Topics: Adolescent; Adult; Aged; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Humans; Interleukin-10; Interleukin-6; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Prognosis; Prospective Studies; Protein Precursors; Shock, Septic; Stem Cell Transplantation; Transplantation, Autologous; Young Adult

To evaluate the tendency of the plasma concentration and clearance of procalcitonin (PCT-c) as biomarkers of prognosis of patients with severe sepsis and septic shock, compared to another early prognosis marker, the number of SIRS criteria at sepsis diagnosis.. We conducted a prospective, observational, cohort study, with patients with severe sepsis and septic shock. The serum procalcitonin was determined at diagnosis of sepsis and after 24 and 48 hours. Demographic data, APACHE IV, SOFA score on arrival, number of SIRS criteria at diagnosis, site of infection and microbiological results were recorded.. Twenty-eight patients were included, 19 clinical and nine surgical. In 13 (46.4%) the source of sepsis was pulmonary, abdominal in seven (25.0%), urinary in five (17.9%) and soft tissue in three cases (10.7%). Fifteen patients had severe sepsis and 13 septic shock. Overall mortality was 17.9% (five patients), three with septic shock. Twenty-eight PCT determinations were performed at sepsis diagnosis, 27 after 24 hours and 26 after 48 hours. The initial concentration was not significantly different between survivors and non-survivors groups, but the differences between the two groups after 24 and 48 hours were statistically significant. There was no difference in the number of SIRS criteria. The 24-hour procalcitonin clearance proved to be significantly higher in the group of survivors (-3.0 versus -300.0, p = 0.028). Although the 48-hour procalcitonin clearance has shown to be higher in the group of survivors when compared to non-survivors, the difference did not reach statistical significance.. Persistently high procalcitonin concentrations in plasma, as well as reduced 24-hours PCT clearence, were associated with a significant increase in mortality in patients with severe sepsis and septic shock.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Male; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

Procalcitonin (ProCT) is increased in serum of septic patients and those with systemic inflammation. Endogenous levels of ProCT might influence the response of polymorphonuclear leukocytes (PMNs), independently of endotoxin, in clinical disease.. Healthy human volunteers.. Recombinant human ProCT (rhProCT).. Whole blood and PMNs were exposed in vitro to exogenous rhProCT. Interleukin (IL)-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNFα), IL-1β, and macrophage inflammatory protein (MIP)-1β (pg/ml) were measured by multiplex suspension bead-array immunoassay, and migration and phagocytosis were measured in PMNs.. In a whole-blood model, a dose-dependent increase in IL-6, TNFα, and IL-1β of the cell-free supernatant was noted. Pre-incubation with ProCT, at doses consistent with clinical sepsis, resulted in a decrease in PMN migration without alteration in phagocytosis of Staphylococcus aureus or indirect measurements of bacterial killing.. Clinically relevant levels of ProCT influence immunologic responses that may contribute to systemic inflammatory response and septic shock.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Chemotaxis, Leukocyte; Cytokines; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Neutrophils; Protein Precursors; Recombinant Proteins; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

Procalcitonin (PCT) concentration of greater than 10 ng/mL is compatible for septic shock. Its predictive value for survival is not well established, mainly because of much overlap and variation of PCT in this condition. We hypothesized that dynamic change of PCT, rather than PCT itself, is predictive of hospital survival when greater than 10 ng/mL. Thirty-seven septic shock patients with PCT concentration of greater than 10 ng/mL were enrolled in this prospective cohort study. Patients were divided into survivors (n = 25) and nonsurvivors (n = 12) based on 28-day hospital outcome. Subsequent PCT measurements were taken 5 days after enrollment. Sequential Organ Failure Assessment (SOFA) scores were recorded simultaneously. Dynamic changes of the PCT and SOFA score were defined as the difference between the subsequent and initial measurement. There were no significant differences between survivors and nonsurvivors in age, sex, initial measurement of PCT, and SOFA. All survivors had a decrease in PCT concentration; median decrease was 9.73 ng/mL. All nonsurvivors had an increase in PCT concentration; median increase was 5.95 ng/mL. Significant decrease in PCT concentration (>25%) was observed in all the 25 survivors, whereas there was none in 12 nonsurvivors. Procalcitonin of initial, subsequent measurements, and dynamics significantly correlated with their counterparts of SOFA score. In conclusion, significant decrease in PCT concentration, rather than PCT concentration itself, may be a useful indicator of survival in septic shock patients when PCT concentration is greater than 10 ng/mL. Procalcitonin concentration highly correlated with the SOFA score in septic shock patients even when the PCT concentration is greater than 10 ng/mL.

Topics: Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; Shock, Septic; Young Adult

A 21-year-old man with signs and symptoms of rapidly progressive shock was admitted to the intensive care unit for treatment of suspected sepsis. Levels of inflammatory markers (including procalcitonin) were highly elevated, but no obvious focus of infection was apparent. Initial sepsis therapy included administration of broad-spectrum antibiotics, vasoconstrictors, and drotrecogin alfa. Cultures of blood, sputum, and urine showed no growth, and no viruses were detected. The random (no stimulation with corticotropin) cortisol level at admission was less than 25 nmol/L. Assays for autoantibodies to the adrenal cortex were strongly positive and confirmed the diagnosis of adrenal failure caused by Addison disease. After initiation of steroid therapy, the patient fully recovered. Although increased procalcitonin levels are considered a reliable and specific indicator of severe generalized infections and bacterial sepsis, elevated procalcitonin levels cannot be relied on when trying to differentiate between addisonian crisis and septic shock.

Topics: Addison Disease; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Fibrinolytic Agents; Humans; Male; Protein C; Protein Precursors; Recombinant Proteins; Shock, Septic; Steroids; Vasoconstrictor Agents; Young Adult

We evaluated the performance of procalcitonin (PCT) and C-reactive protein (CRP) threshold values and kinetics as predictors of ventilator-associated pneumonia (VAP) survival and septic shock development. 45 adult patients with VAP were studied. Serum CRP and PCT levels and the Sequential Organ Failure Assessment (SOFA) score were measured on days 1, 4 and 7 (D1, D4, D7) of VAP and their variations between different days (kinetics) were calculated (DeltaPCT, DeltaCRP). A multivariate logistic regression model was constructed with either VAP 28-day survival or septic shock development as dependent variables, and PCT values, CRP values, kinetics, age, sex, SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II score as independent variables. No difference was found in CRP levels between survivors and nonsurvivors. Nonsurvivors had significantly higher PCT levels on D1 and D7. In the multivariate analysis, the only factors predicting VAP survival were DeltaPCT(7-1) (OR 7.23, 95% CI 0.008-0.468) and DeltaCRP(7-4) (OR 4.59, 95% CI 0.013-0.824). VAP patients who developed septic shock had significantly higher CRP levels on D1 and D7 and higher PCT levels on D1 and D4. The only factor predicting the development of septic shock was SOFA on D1 (OR 7.44, 95% CI 1.330-5.715). Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.

Topics: Adult; Aged; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Pneumonia; Predictive Value of Tests; Protein Precursors; Respiration, Artificial; Shock, Septic

The objective of the paper is to examine the behavior of C-reactive protein (CRP) and procalcitonin (PCT) in the first 12 h of admission and verify which performs better to differentiate children with septic conditions.. Septic children aged between 28 days and 14 years were divided into sepsis (SG; n = 46) and septic shock (SSG; n = 41) groups. CRP and PCT were measured at admission (T0) and 12 h later (T12 h). PCT results were classed as: 0.5 ng/ml = sepsis unlikely; >or=0.5 to <2 = sepsis possible; >or=2 to <10 = systemic inflammation; >or=10 = septic shock.. At T0, there was a higher frequency of SSG with PCT >10 compared to SG [SSG: 30 (73.1%) > SG: 14 (30.4%); P < 0.05]. Similar results were observed at T12 h. Pediatric Risk of Mortality I score was significantly higher for SSG patients with higher PCT than SG patients. CRP levels were not statistically different for groups and time points.. PCT was better than CRP for diagnosing sepsis and septic shock, mainly at admission, and is related to disease severity.

Topics: Adolescent; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

Circulating nucleic acids were discovered more than 60 y ago. With the recent developments in the study of circulating nucleic acids, its application in the diagnostic field has increased. The objective of this study was to assess the usefulness of the quantification of cell-free plasma DNA (CF-DNA) concentration in the diagnosis of infections in febrile patients and as a prognostic marker in septic patients.. Concentrations of CF-DNA, procalcitonin (PCT) and C-reactive protein (CRP) were measured in 110 febrile patients who were clinically diagnosed with fever of unknown origin, localized infection, sepsis or septic shock.. Concentrations of CF-DNA increase according to the severity of the infection. The best cut-off point for predicting infection was 2800 GE (genome equivalents)/mL (sensitivity: 95.0%; specificity: 96.7%) and 14,000 GE/mL for sepsis prediction (sensitivity: 77.8%; specificity: 94.6%). Higher concentrations of CF-DNA were found in exitus septic patients than in survivors. The diagnostic efficiency of CF-DNA was similar to PCT and higher than CRP in infectious processes.. Normal concentrations of CF-DNA can exclude the presence of an infection in febrile patients, and very high concentrations (>10-fold over the normal reference range) stratify the severity of infections, showing a high prognostic value to predict mortality in the absence of other causes for elevated CF-DNA.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; DNA; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Protein Precursors; Seizures, Febrile; Sepsis; Shock, Septic; Young Adult

Topics: Adult; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Therapy, Combination; Female; Humans; Methicillin-Resistant Staphylococcus aureus; Protein Precursors; Shock, Septic; Staphylococcal Infections; Treatment Outcome; Up-Regulation

The diagnosis of adult onset Still's disease is difficult in the absence of definite clinical and laboratory criteria. A delayed diagnosis of adult onset Still's disease was made in a 23-year-old female who developed multi-organ failure and disseminated intravascular coagulation with fingertip auto-amputation during a febrile illness considered septic due to the persistence of elevated serum procalcitonin concentration.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Disseminated Intravascular Coagulation; Female; Humans; Multiple Organ Failure; Protein Precursors; Shock, Septic; Still's Disease, Adult-Onset; Young Adult

Procalcitonin (PCT) is accepted to be a relevant prognostic marker for the development of clinical complications in multiple trauma patients. Therefore, a prospective cohort study was conducted to investigate whether polymorphisms in the calcitonin (CALCA) gene are associated with PCT levels and posttraumatic complications.. During a 14day observation period, blood samples were drawn once daily for systemic PCT concentrations in multiple trauma patients (Injury Severity Score >16). For analysis of allele frequencies, genotype distribution and PCT concentrations polytraumatized patients were separated, according to the development of SIRS, sepsis, septic shock, ARDS, MODS and mortality. Furthermore, association between CALCA polymorphisms and PCT plasma concentrations was assessed.. One hundred thirty seven patients with a mean ISS of 29.2+/-12.1 were included. When trauma patients were grouped according to different posttraumatic complications no association with CALCA SNPs was observed. Additionally, no association was found between CALCA polymorphisms and systemic PCT levels.. CALCA polymorphisms are unlikely to influence clinical outcome in polytraumatized patients. Effects of microbial and inflammatory mediators, as well as other risk factors (gender, age, etc.) seem to have a more significant influence on the transcriptional regulation of CALCA and on PCT plasma concentrations than CALCA polymorphisms.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Female; Gene Frequency; Genotype; Haplotypes; Humans; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Prognosis; Protein Precursors; Respiratory Distress Syndrome; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Young Adult

The Surviving Sepsis Campaign has recommended that antibiotic therapy should be started within the first hour of recognizing severe sepsis. Procalcitonin has recently been proposed as a biomarker of bacterial infection, although the quantitative procalcitonin assay is often time consuming, and it is not always available in many emergency departments (EDs). Our aim is to evaluate usefulness of the semiquantitative procalcitonin fast kit as a guideline for starting antibiotic administration for patients with severe sepsis or septic shock that requires prompt antibiotic therapy in the ED.. We include those patients who were admitted to the ED and who were suspected of having infection. The procalcitonin concentration was determined by semiquantitative PCT-Q strips, and the points of the severity scoring system were calculated. The receiver operating characteristic curve was used to assess the diagnostic value of the PCT-Q strips to predict severe sepsis or septic shock.. Of the 80 recruited patients, 33 patients were categorized as having severe sepsis or septic shock according to the definition. At a procalcitonin cutoff level of 2 ng/mL or greater, the sensitivity of the PCT-Q for detecting severe sepsis or septic shock was 93.94% and the specificity was 87.23. The receiver operating characteristic curve for PCT-Q to predict severe sepsis or septic shock had an area under the curve of 0.916.. PCT-Q is probably a fast, useful method for detecting severe sepsis in the ED, and it can be used as a guideline for antibiotic treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Emergency Service, Hospital; Female; Glycoproteins; Health Status Indicators; Humans; Immunoassay; Infant; Male; Middle Aged; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Young Adult

To assess the clinical value of pro-adrenomedullin (pro-ADM) in the prognosis and risk stratification in sepsis.. Fifty-one critically ill patients admitted to the intensive care unit (ICU) were prospectively stratified into four groups according to internationally recognized criteria: systemic inflammatory response syndrome (SIRS, 25 cases), sepsis (12 cases), severe sepsis (9 cases) and septic shock (5 cases). The levels of plasma pro-ADM was determined in every patient using a new sandwich immunoassay, and compared with procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and the acute physiology and chronic health evaluation II (APACHE II) score.. (1) Median pro-ADM concentration was 0.34 microg/L for SIRS, 2.23 microg/L for sepsis, 4.57 microg/L for severe sepsis and 8.21 microg/L for septic shock. The plasma concentration of pro-ADM exhibited a gradual increase, and the median pro-ADM value was highest in the septic shock group (all P<0.05). (2) Compared with the other biomarkers, in the sepsis, severe sepsis and septic shock groups, the plasma concentration of pro-ADM and APACHE II score in the non-survivors was significantly higher than in the survivors (pro-ADM: 2.01 microg/L vs. 9.75 microg/L, APACHE II score: 23.44 scores vs. 38.21 scores, both P<0.05). (3) By the receiver operating characteristic (ROC) curve plot analysis of pro-ADM in sepsis, the area under the ROC curve for pro-ADM (0.87) in survivors was similar to the area under the ROC curve for PCT (0.81) and APACHE II score (0.81), and was significantly higher than the area under the ROC curve for CRP (0.53) and IL-6 (0.71).. The measurement of pro-ADM is a new and useful marker in sepsis prognosis and risk stratification.

Topics: Adrenomedullin; Adult; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Protein Precursors; Risk Assessment; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

The soluble triggering receptor expressed on myeloid cells (sTREM)-1 has emerged as a potentially useful biomarker for the diagnosis of sepsis. This study aimed to evaluate the prognostic utility of serum sTREM-1 in septic shock, in comparison with that of procalcitonin measurements. Thirty-one consecutive patients in a tertiary medical intensive care unit with septic shock were studied. sTREM-1 levels in blood were measured using a modified immunoblot array technique on days one to three of intensive care unit admission. Serum procalcitonin and interleukin (IL)-1beta, IL-6, IL-IO and tumour necrosis factor-alpha levels were also measured. No significant difference was observed in the sTREM-1 levels on the first three days between survivors and nonsurvivors. sTREM-1 levels moderately correlated with the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on day three, but did not correlate with vasopressor requirements, cytokine levels and the presence of bacteraemia. In contrast, procalcitonin levels were significantly higher in nonsurvivors than in survivors on days two and three. A significant relationship also existed between procalcitonin levels and the other variables. In conclusion, this study found that the prognostic utility of serum sTREM-1 in septic shock is poor and that procalcitonin measurements perform better in this regard.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Female; Humans; Immunoblotting; Interleukins; Male; Membrane Glycoproteins; Middle Aged; Prognosis; Protein Precursors; Receptors, Immunologic; Shock, Septic; Triggering Receptor Expressed on Myeloid Cells-1; Tumor Necrosis Factor-alpha

To assess the potential role of procalcitonin and tumor necrosis factor-alpha, interleukin-6 and interleukin-8, in the prognosis of patients with sepsis.. Prospective study.. The emergency unit of a teaching hospital.. We included 131 patients with sepsis: 15 (12%) with septic shock, 20 (15%) with severe sepsis and 96 (73%) with sepsis.. Out of the 131 patients, 112 (85.5%) survived and 19 (14.5%) died. These two groups of patients differed with regard to simplified acute physiology score II, severity of infectious disease and underlying disease, bacteremia and type of microorganisms. The mean serum levels of tumor necrosis factor, interleukin-6, interleukin-8, procalcitonin and lactates at study entry were higher in nonsurvivors than in survivors. Multivariate regression analysis showed the most significant of these variables to be serum procalcitonin level (P=0.0007), simplified acute physiology score II (P=0.03) and serum lactate level (P=0.03). Using a model incorporating these three variables, with a cut-off value corresponding to a 15% probability of predicting mortality, death could be correctly predicted in 99.5% of cases and survival in 95%. This cut-off value allowed us to maximize the prediction of death. When serum procalcitonin levels were not taken into account, the best model included simplified acute physiology score II and serum lactate and interleukin-6 levels, but the rate of correct prediction of death then dropped to 84%.. Stepwise multivariate logistic regression analysis showed serum procalcitonin level to be a valuable marker of sepsis severity, compared with the 15 other clinical, biochemical and bacteriologic variables tested.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; France; Humans; Interleukin-1; Middle Aged; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Shock, Septic

The biomarkers lactate, procalcitonin, and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are often promoted as being useful for prognostication in septic shock. This study aimed to compare the prognostic utility of these biomarkers with each other and with cytokine measurements and clinical severity scores, and to assess how these biomarkers may be combined to improve their prognostic utility. Seventy-two patients with septic shock were studied. The biomarkers were measured on the first 3 days of stay in the intensive care unit together with serum IL-1beta, IL-6, IL-10, and TNF-alpha levels. Although elevated baseline lactate levels predicted 28-day mortality, elevated procalcitonin and NT-proBNP levels were only predictive from days 2 and 3, respectively. The prognostic utility of baseline lactate levels was poorer than that of baseline cytokine levels, the Acute Physiology and Chronic Health Evaluation II score, and the Sequential Organ Failure Assessment score. However, a rising trend in lactate and procalcitonin levels between days 1 and 2 had superior prognostic utility compared with absolute levels. Indeed, using multivariate analysis, the presence of a concurrent increase in both lactate and procalcitonin levels between days 1 and 2 superseded all cytokine measurements and clinical severity scores as the sole independent predictor of 28-day mortality. In conclusion, elevated baseline lactate levels offer superior prognostic accuracy to baseline procalcitonin levels, which in turn are superior to NT-proBNP levels. To improve their prognostic utility beyond those of cytokine measurements and clinical severity scores, serial lactate and procalcitonin measurements may be combined.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Female; Humans; Lactic Acid; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index; Shock, Septic

Infections and sepsis are major complications in secondary peritonitis and still represent a diagnostic challenge. We hypothesized that the laboratory marker procalcitonin would provide an early and reliable assessment of septic complications.. Prospective, international, multicenter inception cohort study.. Five European surgical referral centers.. Eighty-two patients with intraoperatively proven secondary peritonitis were enrolled within 96 hours of symptom onset.. Procalcitonin and the laboratory routine marker C-reactive protein (CRP) were prospectively assessed and monitored for a maximum of 21 consecutive days.. Procalcitonin concentrations were most closely correlated with the development of septic multiorgan dysfunction syndrome (MODS), with peak levels occurring early after symptom onset or during the immediate postoperative course. No such correlation was observed for CRP. According to receiver operating characteristic analysis, a procalcitonin value of 10.0 ng/mL or greater on 2 consecutive days was superior to a CRP level of 210 mg/L or greater for predicting septic MODS, with sensitivity, specificity, and positive and negative predictive values of 65%, 92%, 83%, and 81% for procalcitonin and 67%, 58%, 49%, and 74% for CRP, respectively (P<.001). Assessment of septic MODS was already possible on the first 2 postoperative days, with similar sensitivity and specificity. Persisting procalcitonin levels greater than 1.0 ng/mL beyond the first week after disease onset strongly indicated nonsurvival and were significantly better than CRP in assessing overall prognosis (P<.001).. Procalcitonin monitoring is a fast and reliable approach to assessing septic MODS and overall prognosis in secondary peritonitis. This single-test marker improves stratification of patients who will develop clinically relevant complications.

Topics: Adult; Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Follow-Up Studies; Glycoproteins; Humans; Luminescent Measurements; Male; Middle Aged; Peritonitis; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; ROC Curve; Severity of Illness Index; Shock, Septic; Time Factors

To investigate plasma high-mobility group box 1 protein (HMGB1) concentration and its relationship with organ dysfunction and outcome in septic shock patients.. Prospective, noninterventional study. Medical adult intensive care unit at a university hospital in France.. 42 critically ill patients with septic shock.. Arterial blood was drawn within 12 h of admission for the measurement of plasma HMGB1 concentration by ELISA. Repeated sampling was performed on days 3, 7, and 14.. Median HMGB1 concentration was 4.4 ng/ml (IQR 1.2-12.5) at admission, with no difference between survivors and nonsurvivors. A positive correlation was observed between HMGB1 and SOFA score and lactate, and procalcitonin concentrations. There was a progressive but statistically nonsignificant decline in HMGB1 concentration among the survivors, while nonsurvivors showed an increase in HMGB1 level between days 1 and 3. SOFA score and lactate and procalcitonin concentrations did not vary significantly between days 1 and 3. When measured on day 3, HMGB1 discriminated survivors from nonsurvivors with 66% sensitivity and 67% specificity, and concentration greater than 4 ng/ml was associated with an odds ratio of death of 5.5 (95% CI 1.3-23.6).

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Female; France; HMGB1 Protein; Humans; Inflammation; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; Shock, Septic

The main causes of complications of allogenic hematopoietic stem cell transplantation are infections and graft versus host disease.. To assess the predictive value of C reactive protein (CRP) and procalcitonin (PCT) in the diagnosis of invasive bacterial infections in children with febrile neutropenia after an allogenic hematopoietic stem cell transplantation.. Prospective follow up of patients aged 18 years or less, with febrile neutropenia after an allogenic hematopoietic stem cell transplantation. In all patients, cultures from sterile sites, CRP and PCT determinations were done. CRP levels were also measured prior to transplantation and three times per week for 30 days after the procedure. An independent evaluator, blinded to the results of CRP and PCT, classified children as with or without invasive bacterial infection.. Thirty three patients aged 9+/-5 years (21 males) were studied. Eight had an invasive bacterial infection. Sensitivity, specificity, positive and negative predictive values of a CRP > or = 90 mg/L for the diagnosis of invasive bacterial infection were 25, 80, 29 and 77%, respectively. The figures for a PCT > or = 0.7 ng/ml were 43, 78, 38 and 82%, respectively. No differences in repeated CRP values measured during evolution, were observed.. A CRP > or = 90 mg/L or a PCT > or = 0.7 ng/ml had a high specificity and negative predictive value but low sensitivity for the diagnosis of invasive bacterial infections in recipients of allogenic hematopoietic stem cell transplantation.

Topics: Adolescent; Anti-Infective Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Male; Neutropenia; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

To assess whether different diagnostic and prognostic cutoff values of procalcitonin should be considered in surgical and in medical patients with septic shock.. Prospective observational study.. Intensive care unit of the Avicenne teaching hospital, France.. All patients with septic shock or noninfectious systemic inflammatory response syndrome within 48 hrs after admission.. None.. Patients were allocated to one of the following groups: group 1 (surgical patients with septic shock), group 2 (surgical patients with noninfectious systemic inflammatory response syndrome), group 3 (medical patients with septic shock), and group 4 (medical patients with noninfectious systemic inflammatory response syndrome). Procalcitonin at study entry was compared between group 1 and group 2 and between group 3 and group 4 to determine the diagnostic cutoff value in surgical and in medical patients, respectively. Procalcitonin was compared between survivors and nonsurvivors from group 1 and group 3 to determine its prognostic cutoff value. One hundred forty-three patients were included: 31 in group 1, 36 in group 2, 36 in group 3, and 40 in group 4. Median procalcitonin levels (ng/mL [interquartile range]) were higher in group 1 than in group 3 (34.00 [7.10-76.00] vs. 8.40 [3.63-24.70], p = .01). In surgical patients, the best diagnostic cutoff value was 9.70 ng/mL, with 91.7% sensitivity and 74.2% specificity. In medical patients, the best diagnostic cutoff value was 1.00 ng/mL, with 80% sensitivity and 94% specificity. Procalcitonin was a reliable early prognostic marker in medical but not in surgical patients with septic shock. A cutoff value of 6.00 ng/mL had 76% sensitivity and 72.7% specificity for separating survivors from nonsurvivors.. The diagnostic cutoff value of procalcitonin was higher in surgical than in medical patients. Early procalcitonin was of prognostic interest in medical patients.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Confidence Intervals; Diagnosis, Differential; Disease Progression; Female; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Probability; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index; Shock, Septic; Survival Analysis; Systemic Inflammatory Response Syndrome; Treatment Outcome

A 64-year-old male with an APC resistance (factor V mutation Leiden) and interrupted oral anticoagulation due to an erosive gastritis, was admitted to hospital for increasing dyspnoea. Transthoracic echocardiography revealed a floating thrombus via an open foramen ovale in both atria reaching both ventricles. Sonography showed multiple stage thrombosis of the left leg reaching to the V. femoralis superficialis. A few months previously, peripheral pulmonary artery embolization has been confirmed by scintigraphy. The patient was transferred to our hospital and underwent emergency surgery for closure of the atrial septum defect and thrombus removal. On the 4th postoperative day, the patient was transferred to the normal ward, however, on the 10th postoperative day, the patient developed a symptomatic transitory psychotic syndrome and became hypotensive before he was transferred to the ICU. Due to impaired oxygenation and the patient's history, a new pulmonary artery embolization was suspected. After ICU admission, the patient required increasing norepinephrine support and rapidly developed septic fever. However, serum procalcitonin was elevated and a computed tomography (skull, chest and abdomen) was performed for a focus search. Pulmonary artery embolism could be ruled out but an oval structure near to the ampulla recti (ca. 30 x 20 mm) was identified as an abscess and immediate abscess incision was performed. After surgery, the further course was characterized by a steep fall in vasopressor support and body temperature. The patient was transferred to the normal ward on the 2nd postoperative day. This case shows that procalcitonin allows early and reliable diagnosis of sepsis in patients with undefined shock.

Topics: Activated Protein C Resistance; Anticoagulants; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Critical Care; Heart Septal Defects, Atrial; Humans; Male; Middle Aged; Protein Precursors; Psychoses, Substance-Induced; Sepsis; Shock, Septic

The diagnostic value of procalcitonin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-10 levels in differentiating sepsis from severe sepsis and the prognostic value of these levels in predicting outcome were evaluated and compared in patients with community-acquired sepsis, severe sepsis, and septic shock in the first 72 h of admission to the hospital. Thirty-nine patients were included in the study. The severe sepsis and septic shock cases were combined in a single "severe sepsis" group, and all comparisons were made between the sepsis (n=21 patients) and the severe sepsis (n=18 patients) groups. Procalcitonin levels in the severe sepsis group were found to be significantly higher at all times of measurements within the first 72 h and were significantly higher at the 72nd hour in patients who died. Procalcitonin levels that remain elevated at the 72nd hour indicated a poor prognosis. C-reactive protein levels were not significantly different between the groups, nor were they indicative of prognosis. No significant differences in the levels of tumor necrosis factor-alpha were found between the sepsis and severe sepsis groups; however, levels were higher at the early stages (at admission and the 24th hour) in patients who died. Interleukin-10 levels were also higher in the severe sepsis group and significantly higher at all times of measurement in patients who died. When the diagnostic and prognostic values at admission were evaluated, procalcitonin and interleukin-10 levels were useful in discriminating between sepsis and severe sepsis, whereas tumor necrosis factor-alpha and interleukin-10 levels were useful in predicting which cases were likely to have a fatal outcome.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Female; Humans; Interleukin-10; Male; Middle Aged; Prognosis; Protein Precursors; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

To assess the effectiveness of different procalcitonin cutoff values to distinguish non-infected (negative+SIRS) from infected (sepsis+severe sepsis+septic shock) medical and surgical patients.. PCT plasma concentration was measured using an automated chemiluminescence analyzer in 1013 samples collected in 103 patients within 24 h of admission in ICU and daily during the ICU stay. We compared PCT levels in medical and surgical patients. We also compared PCT plasma levels in non-infected versus infected patients and in SIRS versus infected patients both in medical and in surgical groups.. Median values of PCT plasma concentrations were significantly higher in infected than in non-infected groups, both in medical (3.18 vs. 0.45 microg/L) (p<0.0001) and in surgical (10.45 vs. 3.89 microg/L; p<0.0001) patients. At the cutoff of 1 microg/L, the LR+ was 4.78, at the cutoff of 6 microg/L was 12.53, and at the cutoff of 10 microg/L was 18.4.. This study highlights the need of different PCT cutoff values in medical and surgical critically ill patients, not only at the ICU admission but also in the entire ICU stay.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Male; Middle Aged; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

To compare procalcitonin, lactate, and C-reactive protein as prognostic markers in children with meningococcal septic shock.. Prospective observational study.. Alder Hey Children's Hospital, Liverpool, UK.. Children admitted to our hospital during a 16-month period with a diagnosis of meningococcal sepsis.. Plasma procalcitonin at admission was significantly higher in children with septic shock (median, 73.80 vs. 16.44 ng/mL), those requiring ventilation (median, 47.02 vs. 12.00 ng/mL), and those with a duration of hospital stay >10 days (median, 131.35 vs. 19.26 ng/mL). Both procalcitonin and lactate reliably discriminated between those children with septic shock (area under the curve [AUC] = 0.85 and 0.84, respectively) and durations of hospital stay exceeding 10 days (AUC = 0.87 and 0.79, respectively) and those without, but C-reactive protein did not. Procalcitonin alone reliably discriminated between those children requiring ventilation and those who did not (AUC = 0.72).. Procalcitonin is a reliable prognostic marker of septic shock, requirement for ventilation, and prolonged hospital stay in children with meningococcal sepsis and performs better than lactate and C-reactive protein.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Critical Care; Hospital Mortality; Humans; Lactic Acid; Length of Stay; Meningococcal Infections; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Respiration, Artificial; Shock, Septic; Survival Rate

A 22 year old female was admitted to the emergency department with high fever up to 41,5 degrees C, tachycardia, and arterial hypotension. Clinically, she presented with bilateral pulmonary coarse crackles. Diagnosis on admission was pneumonia with septic shock. Intriguingly, procalcitonin (PCT) was increased early, reaching up to 435 ng/mL, while C-reactive protein levels were only moderately increased, with several days delay. The sepsis was originated from a multi-resistant pseudomonas aeruginosa pneumonia. Remarkably, the course of PCT levels reflected the severity of septic shock in that it paralleled noradrenaline demand. Ten months previously, the patient had been diagnosed with acute disseminated brainstem encephalitis (ADEM), and had received two cycles of intravenous cyclophosphamide. Our case illustrates that PCT is an early marker for sepsis and it indicates that PCT may also be a valuable marker for the severity of sepsis in immunosuppressed patients.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Immunosuppression Therapy; Norepinephrine; Pneumonia, Bacterial; Protein Precursors; Pseudomonas Infections; Sepsis; Shock, Septic

To determine whether procalcitonin is a reliable diagnostic and prognostic marker in septic shock compared with nonseptic shock.. Prospective controlled trial.. Intensive care unit of the Avicenne Teaching Hospital, Bobigny, France.. All patients admitted to our intensive care unit over a 12-month period with clinical evidence of shock.. None.. Echocardiography or pulmonary artery flotation catheter measurements were used to assess hemodynamics, and multiple specimens were obtained for microbiological studies. Standard criteria were used to diagnose septic shock. Serum concentrations of procalcitonin, C-reactive protein, and lactate were determined on the day of shock onset (day 1) and on days 3, 7, and 10. Seventy-five patients were included, 62 in the septic shock group and 13 in the cardiogenic shock group. Serum procalcitonin on day 1 was significantly higher in patients with than without septic shock (median, 14 [0.3-767] ng/mL vs. 1 [0.5-36] ng/mL, p < .01). A cutoff value of 1 ng/mL had 95% sensitivity and 54% specificity for separating patients with and without sepsis. C-reactive protein failed to discriminate between these two groups. Among patients with sepsis, procalcitonin concentrations were significantly higher in those who died than in the survivors, at all four measurement time points (median, 16 [0.15-767] ng/mL vs. 6 [0.2-123] ng/mL, p = .045 on day 1; 6.5 [0.3-135] ng/mL vs. 1.05 [0.11-53] ng/mL, p = .02 on day 10). A cutoff value of 6 ng/mL on day 1 separated patients who died from those who survived with 87.5% sensitivity and 45% specificity. C-reactive protein was not helpful for predicting mortality. Serum lactate was a nonspecific prognostic marker.. These data indicate that procalcitonin may be a valuable early diagnostic and prognostic marker in patients with septic shock.

Topics: Adult; Aged; APACHE; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Discriminant Analysis; Female; France; Hospitals, Teaching; Humans; Lactic Acid; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Respiration, Artificial; Sensitivity and Specificity; Shock, Cardiogenic; Shock, Septic; Survival Analysis; Time Factors

To define whether procalcitonin should be introduced in the diagnostic criteria of sepsis.. Procalcitonin was estimated in sera of 105 critically ill patients by an immunochemiluminometric assay. Diagnosis was settled by 3 types of criteria: A, the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) 1992 criteria; B, the ACCP/SCCM criteria and concentrations of procalcitonin above 1.0 ng/mL as indicative of SIRS/sepsis; and C, the ACCP/SCCM criteria and concentrations of procalcitonin 0.5 to 1.1 ng/mL for SIRS and above 1.1 ng/mL for sepsis.. Criteria A identified 50.5% of patients with SIRS, 18.1% with sepsis, 0.9% with severe sepsis and 22.9% with septic shock; respective diagnosis by criteria B were 26.7%, 9.5%, 10.5% and 25.7%; and respective diagnosis by criteria C were 19.0%, 25.7%, 9.5%, and 25.7%. Sensitivity of concentrations between 0.5 ng/mL and 1.1 ng/mL was 25.6% for Systemic Inflammatory Response Syndrome (SIRS); and above 1.1 ng/mL 92.8% for sepsis. Sepsis-related death was associated with elevated procalcitonin upon presentation of a clinical syndrome.. Despite the limited diagnostic value of procalcitonin for SIRS, concentrations of procalcitonin above 1.1 ng/mL are highly indicative for sepsis without, however, excluding the presence of SIRS.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Severity of Illness Index; Shock, Septic; Systemic Inflammatory Response Syndrome

To investigate the correlation between microalbuminuria and extravascular lung water in patients in septic shock who require mechanical ventilation for severe respiratory failure.. Prospective, observational, clinical study in the 20-bed intensive care unit of a university hospital.. 25 consecutive patients in septic shock and also in severe respiratory failure requiring mechanical ventilation.. Hemodynamic parameters and extravascular lung water were determined by single arterial thermodilution. Together with each hemodynamic measurement the PaO(2)/FIO(2) ratio and urinary microalbumin to creatinine ratio (M:Cr) was measured. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were also determined daily.. The EVLW index was significantly higher than normal throughout the study. Microalbuminuria was in the normal range on entry and remained so for the rest of the study period. Serum PCT and CRP levels were significantly higher than normal at every assessment points. No significant correlation was found between M:Cr and either EVLW or PaO(2)/FIO(2).. In this study patients in septic shock with significantly elevated EVLW had normal urinary M:Cr, and there was no correlation between M:Cr and EWLV, and PaO(2)/FIO(2). Therefore based on the current results routine measurements of microalbuminuria to determine endothelial permeability cannot be recommended in critically ill patients.

Topics: Aged; Albuminuria; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Capillary Permeability; Creatinine; Extravascular Lung Water; Female; Hemodynamics; Humans; Linear Models; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; Respiration, Artificial; Respiratory Insufficiency; Shock, Septic; Statistics, Nonparametric; Thermodilution

To examine the relationships between procalcitonin, bacterial infection, sepsis-induced multiple organ failure, and mortality rate in children.. Cohort study.. A multidisciplinary, tertiary-care pediatric intensive care unit.. Seventy-eight children meeting criteria for sepsis or septic shock and 12 critically ill children without sepsis.. Venous or arterial blood sampling.. Demographic, epidemiologic, and outcome data were recorded. Plasma from children with sepsis were collected on days 1 and 3, and procalcitonin concentrations were measured by immunoluminometric assay. Organ failure index scores were determined, and multiple organ failure was defined as organ failure index > or = 3. Persistent multiple organ failure was defined by presence of multiple organ failure on day 3. Procalcitonin concentrations (median [25th percentile-75th percentile]) were increased among children with sepsis on day 1 (2.4 ng/mL [0.2-24.2], p < .01) but not on day 3 (0.8 ng/mL [0.1-8.1], p = nonsignificant) vs. controls (0.2 ng/mL [0.1-0.5]). This increase in procalcitonin concentration was particularly robust among children with bacterial sepsis on day 1 (7.1 ng/mL [0.9-44.8], p < .001) and on day 3 (2.9 ng/mL [0.1-32.4], p < .05). Procalcitonin concentrations were not increased among children with fungal, viral, or culture-negative sepsis vs. controls. Procalcitonin concentrations were persistently increased over time among patients with bacterial sepsis who had persistent multiple organ failure (p < .05) and who died (p < .01) but not among patients with nonbacterial sepsis.. Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Further study is needed to better delineate this differential procalcitonin response to bacterial vs. nonbacterial sepsis and to characterize any mechanistic role that procalcitonin might play in the development of bacterial sepsis-induced multiple organ failure and mortality.

Topics: Adolescent; Analysis of Variance; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Multiple Organ Failure; Protein Precursors; Sepsis; Shock, Septic

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Intensive Care Units, Pediatric; Predictive Value of Tests; Protein Precursors; Sepsis; Shock, Septic

We analysed the clinical value of the procalcitonin quick test (PCT-Q; BRAHMS Diagnostica, GmbH, Berlin) in infected pancreatic necrosis verified by guided fine-needle aspiration (FNA). In a prospective, controlled study the results of 24 patients were evaluated during 2001. PCT-Q test was performed in patients with necrosis verified on CT scan and/or septic symptoms. If PCT-Q test was positive or septic complication (infected necrosis or abscess) developed CT or US guided fine-needle aspiration was performed with Gram staining and bacterial culture of the sample. Positive FNA result was indication for surgery with repeated staining and bacterial culture of the surgical specimen. Septic complications of pancreatic origin developed in 12 patients. Comparing the results fine-needle aspiration was more authentic with a sensitivity of 92% and a specificity of 100%, while the sensitivity of the PCT-Q test remained 75% and its specificity 83%. Comparing abscess and infected necrosis, significantly higher procalcitonin values were detected in patients with necrosis. These results show that PCT-Q test can be a possible non-invasive method besides fine-needle aspiration. Elevated levels of procalcitonin (higher than 2 ng/ml) clearly suggest infection of the necrosis, while lower values do not exclude the possibility of local septic progression.

Topics: Acute Disease; Adult; Aged; Bacterial Infections; Biomarkers; Biopsy, Needle; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pancreatitis; Pancreatitis, Acute Necrotizing; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index; Shock, Septic

We prospectively evaluated the capacity of serum procalcitonin (PCT), compared with serum levels of C-reactive protein (CRP) and endotoxin, to identify children at high risk for mortality from sepsis after BMT. Of 47 pediatric bone marrow transplantation patients studied, 22 had an uneventful course post-transplant (Group 1), 17 survived at least one septic event (Group 2), and eight died from multiorgan failure (MOF) following septic shock (Group 3). Median concentrations of PCT over the course of the study were 1.3, 15.2, and 102.8 ng/ml, respectively, in each of the three groups (P<0.002 for each comparison). Median concentrations of CRP were 91, 213, and 260 mg/l, respectively (P<0.001 for Group 1 vs Group 2 and Group 3; P=NS for Group 2 vs Group 3). Median concentrations of endotoxin were 0.21, 0.30, and 0.93 U/l, respectively (P=NS for each comparison). Median concentrations of PCT, in contrast to serum CRP and endotoxin, correlated with the severity of sepsis (8.2 ng/ml in 'sepsis' and 22.3 ng/ml in 'severe sepsis', P=0.028) and provided useful prognostic information during septic episodes.

Topics: Adolescent; Adult; Bone Marrow Transplantation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Endotoxins; Female; Germany; Humans; Infant; Male; Multiple Organ Failure; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Sepsis; Shock, Septic

One of the most difficult tasks in differential diagnosis of patients with septic syndrome at the Intensive Care Units is to differentiate between infection and non-infection etiology of this syndrome. In the last years, new parameters have played an important role in this area--C-reactive protein, Interleukin-6 and procalcitonin.. Of the investigation was to compare these three parameters in differential diagnosis of the septic syndrome. THE COHORT AND METHODS: The authors examined 56 patients (17 women and 39 men, mean age being 43 and 51 years, respectively) hospitalized at the Intensive Care Units who corresponded to the criteria of the syndrome of inflammatory response, sepsis or septic shock. A total of 99 examinations were done. The samples were taken up to 24 hours after the beginning of clinical symptomatology and submitted to the laboratory within four hours. Immediately afterwards the determination of concentrations of all three parameters--C-reactive protein, interlaukin-6 and procalcitonin, were done. The results of the examinations were compared to each other as well as to the diagnosis of sepsis--the confirmed infection etiology.. In all the evaluated parameters the authors detected significant differences between the values of entry examination and all measurements between the patients with the syndrome of systemic inflammatory response and septic shock as well as among patients with sepsis and the septic shock. Likewise, the authors confirmed significant differences between concentrations of all three parameters in comparing the patients with sepsis and those with the septic shock. Only in the case of procalcitonin there was a significant difference in concentration between patients with the syndrome of systemic inflammatory response of non-infectious etiology and those with sepsis. The concentration of procalcitonin was the only predictive marker of diagnosis with the correlation coefficient r = 0.7263, r2 = 0.5275, P < 0.00005.. Calcitonin proved to be the most specific parameter in demonstrating infection etiology in patients with the septic syndrome, its predictive value being higher than that of C-reactive protein and Interleukin-6. Monitoring of calcitonin dynamism provides important information on efficiency of the applied antibiotic treatment. In patients with diagnostic uncertainties as far as the etiology of the septic syndrome is concerned; procalcitonin is the parameter of choice, while it may be supplemented with the examination of C-reactive protein.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

To measure the mass transfer and clearance of procalcitonin (PCT) in patients with septic shock during continuous venovenous hemofiltration (CVVH), and to assess the mechanisms of elimination of PCT.. The medical department of intensive care.. A prospective, observational study.. Thirteen critically ill patients with septic shock and oliguric acute renal failure requiring continuous venovenous postdilution hemofiltration with a high-flux membrane (AN69 or polyamide) and a 'conventional' substitution volume (< 2.5 l/hour).. PCT was measured with the Lumitest PCT Brahms(R) in the prefilter and postfilter plasma, in the ultrafiltrate at the beginning of CVVH (T0) and 15 min (T15'), 60 min (T60') and 6 hours (T6h) after setup of CVVH, and in the prefilter every 24 hours during 4 days. Mass transfer was determined and the clearance and the sieving coefficient were calculated according to the mass conservation principle. Plasma and ultrafiltrate clearances, respectively, at T15', T60' and T6h were 37 +/- 8.6 ml/min (not significant) and 1.8 +/- 1.7 ml/min (P < 0.01), 34.7 +/- 4.1 ml/min (not significant) and 2.3 +/- 1.8 ml/min (P < 0.01), and 31.5 +/- 7 ml/min (not significant) and 5 +/- 2.3 ml/min (P < 0.01). The sieving coefficient significantly increased from 0.07 at T15' to 0.19 at T6h, with no difference according to the nature of the membrane. PCT plasma levels were not significantly modified during the course of CCVH.. We conclude that PCT is removed from the plasma of patients with septic shock during CCVH. Most of the mass is eliminated by convective flow, but adsorption also contributes to elimination during the first hours of CVVH. The effect of PCT removal with a conventional CVVH substitution fluid rate (<2.5 l/hour) on PCT plasma concentration seems to be limited, and PCT remains a useful diagnostic marker in these septic patients. The impact of high-volume hemofiltration on the PCT clearance, the mass transfer and the plasma concentration should be evaluated in further studies.

Topics: Acute Kidney Injury; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Hemofiltration; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Shock, Septic

To study changes in proinflammatory markers and mediators in septic shock in patients with hematologic malignancy (HM).. The examination of 33 patients with HM and septic shock included measurement of plasma concentrations of tumor necrosis factor (TNF), interleukine-6 (IL-6), endotoxin, procalcitonin (PCT) 12-24 hours before and each 12 hours after shock; registration of central hemodynamics parameters, the condition severity by APACHE II.. Out of 33 patients 18 died of refractory shock, 15 survived the shock. Within the first shock hour TNF fell from 571.2 +/- 195 to 115.8 +/- 71.1 pg/ml (p < 0.02), later being stable. In those who died and survived TNF was the same. IL-6 fall was seen 36 hours after shock and was observed in the survivors; in those who died IL-6 was unchanged. Endotoxin in the blood was detected in 21 of 33 patients. In the survivors endotoxinemia declined after 2 days of treatment. 72 hours after beginning of the shock the survivors had no endotoxin. In shock APACH II severity of the patient's condition was graver in patients with endotoxinemia than without it (31.6 +/- 1.6 and 28.1 +/- 1.6 scores, p < 0.05). Blood endotoxin levels and APACHE II scores correlated (r = 0.24, p < 0.05) positively and negatively with deficiency of buffer bases (r = -0.29, p < 0.05) and blood pH) r = -0.3, p < 0.05), left ventricular contractility index (r = -0.46, p < 0.01) and right ventricle (r = -0.52, p < 0.01), mean AP (r = -0.22, p < 0.03). PCT concentration was lower before shock than on its hour 1 (4.2 +/- 2.9 and 6.9 +/- 1.1 ng/ml, p < 0.05). No significant changes in PCT were found later.. PCT is a specific marker of a severe infection. Rapid elimination from the blood of TNF and IL-6 makes them inadequate in sepsis diagnosis. Endotoxinemia aggravates the patients condition. Positive LAL-test results were obtained in gram-negative and fungal infections.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Female; Hematologic Neoplasms; Humans; Interleukin-6; Male; Prospective Studies; Protein Precursors; Shock, Septic; Tumor Necrosis Factor-alpha

High levels of tumor necrosis factor (TNF) alpha messenger RNAs and interleukin (IL) 8 have been reported in leukocytes of patients with sepsis.. Assessment of leukocyte intracytoplasmic levels of proinflammatory and anti-inflammatory cytokines might be clinically more relevant to determine prognosis in patients with severe sepsis.. Cohort study.. Surgical intensive care units of a university hospital.. Leukocyte suspensions obtained from 16 patients, 6 during early sepsis or septic shock and 10 during late sepsis or septic shock, were incubated with anti-CD14 and anti-CD2 or anti-CD3 monoclonal antibodies and then with intracytoplasmic anticytokine antibodies staining for interferon-gamma, TNF-alpha, IL-2, IL-6, IL-8, IL-10, and IL-12 and analyzed with a flow cytometer.. Mann-Whitney test and Spearman correlation test were used in statistical evaluations according to the 28-day all-cause mortality rates and multiple organ dysfunction and sepsis-related organ failure assessment scores.. Higher serum IL-6, IL-8, C-reactive protein, and procalcitonin levels were found in patients with high multiple organ dysfunction and sepsis-related organ failure assessment scores (greater than or equal to the median values [8 and 11, respectively]), in contrast to decreased T-lymphocyte-associated IL-6 and TNF-alpha and monocyte-associated IL-10 and IL-12 proportions. Furthermore, in 28-day all-cause mortality analysis, there were higher levels of C-reactive protein and procalcitonin in nonsurvivors (n = 9) than in survivors (n = 7), while T-lymphocyte-associated IL-2, IL-6, IL-10, and TNF-alpha and monocyte-associated IL-10 and TNF-alpha proportions decreased in the nonsurvivors.. These results suggest that diminished lymphocyte- and monocyte-associated proinflammatory and anti-inflammatory cytokine levels are associated with worse prognosis in patients with severe sepsis.

Topics: APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Glycoproteins; Humans; Interferon-gamma; Interleukins; Leukocytes; Male; Middle Aged; Monocytes; Protein Precursors; Sepsis; Shock, Septic; T-Lymphocytes; Tumor Necrosis Factor-alpha

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Humans; Meningococcal Infections; Prognosis; Protein Precursors; Sensitivity and Specificity; Shock, Septic

To assess the prognostic value of procalcitonin levels during the clinical course of meningococcal disease in children.. A retrospective, descriptive study.. University paediatric intensive care unit.. Nine patients with meningococcal sepsis and 55 patients with meningococcal septic shock were included in the study, giving a total of 64.. Procalcitonin (PCT), C-reactive protein (CRP), cytokines (IL-6, IL-8 and TNF-alpha), plasminogen activator inhibitor-1 (PAI-1) and several routine laboratory parameters were determined and expressed as medians (ranges). PCT levels on hospitalisation were elevated in all children as compared to normal values. Median PCT levels on admission were significantly higher in children with septic shock than in children with sepsis (270 ng/ml (5.7-672.3) versus 64.4 (20.6-283.7); p<0.01). When the patients were categorised to severity using the Pediatric Risk of Mortality (PRISM) score (group 1: <15 points, group 2: 16-30, group 3: >30), the PCT levels were significantly different in the three groups. All markers, with the exception of PCT (p=0.056), were significantly different between survivors and non-survivors. When the duration of petechiae was taken into account, the difference in PCT levels became significant (p=0.04).. Procalcitonin levels on admission are related to severity. In the case of a short disease history (duration of petechiae), PCT levels are also related to mortality. Although PCT levels are elevated in all patients, the levels per se do not allow a prediction about survival versus non-survival, this is in contrast to other markers and scores (PRISM).

Topics: Adolescent; Area Under Curve; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cytokines; Female; Humans; Infant; Male; Meningococcal Infections; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prognosis; Protein Precursors; Retrospective Studies; Shock, Septic; Statistics, Nonparametric

Procalcitonin (PCT) is increasingly recognised as an important diagnostic parameter in clinical evaluation of the critically ill. This prospective study was designed to investigate PCT as a diagnostic marker of infection in critically ill patients with sepsis. Eighty-five adult ICU patients were studied. Four groups were defined on the basis of clinical, laboratory and bacteriologic findings as systemic inflammatory response syndrome (SIRS) (n = 10), sepsis (n = 16), severe sepsis (n = 18) and septic shock (n = 41). Data were collected including C-reactive protein (CRP), PCT levels and Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores on each ICU day. PCT levels were significantly higher in patients with severe sepsis and septic shock (19.25 +/- 43.08 and 37.15 +/- 61.39 ng/ml) than patients with SIRS (0.73 +/- 1.37 ng/ml) (P < 0.05 for each comparison). As compared with SIRS patients, plasma PCT levels were significantly higher in infected patients (21.9 +/- 47.8 ng/ml), regardless of the degree of sepsis (P < 0.001). PCT showed a higher sensitivity (73% versus 35%) and specificity (83% versus 42%) compared to CRP in identifying infection as a cause of the inflammatory response. Best cut-off levels were 1.31 ng/ml for PCT and 13.9 mg/dl for CRP. We suggest that PCT is a more reliable marker than CRP in defining infection as a cause of systemic inflammatory response.

Topics: Adult; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

To determine the relationship between plasma procalcitonin (PCT) levels, C-reactive protein (CRP), white blood cell count (WBC), ionized calcium (Ca2+), and patient outcome; and to compare the diagnostic and prognostic information provided by PCT and by CRP.. Prospective, observational study.. Intensive care unit.. Fifty-three patients with septic shock, consecutively diagnosed according to consensus guidelines.. None.. Blood was sampled at diagnosis and 24 and 48 hrs later and in a subgroup (n = 23) after 120 hrs. PCT was measured with LUMItest and CRP with Vitros slides. Ca2+ was calculated according to McLean-Hastings from calcium and protein levels on Vitros. In all 53 patients, PCT and CRP were elevated (>0.5 ng/mL and >10 mg/L, respectively) within 24 hrs after diagnosis. Nonsurvivors (n = 25) were older (p <.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p =.02) at diagnosis but did not differ in sepsis etiology, medical history, sex ratio, levels of PCT, CRP, and Ca2+, or WBC count at any time point. Using logistic regression, initial PCT levels were correlated with CRP values (p =.001) and APACHE II score (p <.05), but not with age, gender, Ca2+ levels, survival, or type of pathogen. Within 48 hrs, however, PCT levels decreased more frequently from baseline in survivors than in nonsurvivors (80% vs. 41%, p <.05). Likewise, CRP levels decreased more often in survivors (100% vs. 64%, p <.05) but only at 120 hrs.. PCT levels were correlated with the severity of disease at onset (APACHE II) and inflammation (CRP) but not with Ca2+ levels. Inaugural PCT or CRP levels per se poorly predicted outcome but decreasing levels were associated with a higher probability of survival. In this respect, PCT was found to be an earlier marker than CRP.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Calcium; Female; Humans; Intensive Care Units; Leukocyte Count; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Shock, Septic

Procalcitonin (PCT). a new marker proposed as a diagnostic tool for bacterial infections, triggers a systemic-inflammatory reaction in the body (sepsis, septic shock) and has potential use in a wide range of patient settings. To interpret the results from PCT measurements, we depend on reference intervals established from relevant populations. PCT and C-reactive protein (CRP) concentrations were analysed in 47 patients with a normal postoperative course after major abdominal surgery. The mean concentration of PCT declines from the first day and reaches half its initial values on the second day after the operation. whereas the mean concentration of CRP increases in the first 48 h and reaches half its maximum value on the fifth day after the operation. We present a continuous reference interval for plasma PCT and CRP concentrations in the first week following major abdominal surgery. For PCT we also present a graphic display of expected mean and expected upper reference limits predicted from the value measured on the first postoperative day.

Topics: Abdomen; Abscess; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chemistry, Clinical; Humans; Pancreatitis, Acute Necrotizing; Peritonitis; Pneumonia; Postoperative Complications; Protein Precursors; Reference Values; Shock, Septic

Only two cases of adult-onset Still's disease associated with shock have been previously described. We report a case of shock in a man with adult-onset Still's disease and discuss the relationship between the two processes by assessing tumor necrosis factor-alpha, procalcitonin and interleukin-6 concentrations.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Fatal Outcome; Humans; Interleukin-6; Male; Middle Aged; Protein Precursors; Shock, Septic; Still's Disease, Adult-Onset; Tumor Necrosis Factor-alpha

Topics: Animals; Anti-Inflammatory Agents; Blood Cells; Calcitonin; Calcitonin Gene-Related Peptide; Cricetinae; Humans; Inflammation; Lipopolysaccharides; Mesocricetus; Muscle, Smooth, Vascular; Protein Precursors; Rats; RNA, Messenger; Shock, Septic; Tumor Necrosis Factor-alpha

Procalcitonin (PCT) has proven to be a very sensitive marker of sepsis for non-leucopenic patients. Little is known about its relevance in immunosuppressed and leucopenic adults. Four hundred and seventy-five PCT determinations were carried out in 73 haematological patients: on 221 occasions the white blood cell (WBC) count was < 1.0 x 10(9)/l and on 239 occasions it was > 1.0 x 10(9)/l leucocytes. Patients were classified as: non-systemic infected controls (n = 280), patients with bacteraemia (n = 32), sepsis (n = 30), severe sepsis (n = 3), septic shock (n = 3) and systemic inflammatory response syndrome (SIRS) (n = 62). When the WBC count was > 1.0 x 10(9)/l, gram-negative bacteria induced higher PCT levels (median 9.4 ng/ml) than gram-positives (median 1.4 ng/ml). In cases with a WBC < 1.0 x 10(9)/l, PCT levels were similar for gram-negative and gram-positive bacteria (1.1 ng/ml versus 0.85 ng/ml). Regardless of the leucocyte count, the median PCT level in bacteraemia cases always remained < 0.5 ng/ml. In heavily leucopenic situations, PCT levels were never > 2 ng/ml even in the sepsis and severe sepsis/septic shock groups, whereas a WBC count > 1.0 x 10(9)/l resulted in median PCT values of 4.1 ng/ml and 45 ng/ml respectively. The positive predictive value for sepsis (cut-off 2 ng/ml) was 93% in cases of WBC count > 1.0 x 10(9)/l, but only 66% in leucopenic conditions. The negative predictive value (cut-off 0.5 ng/ml) was 90% when the WBC count was > 1.0 x 10(9)/l and 63% in leucopenic conditions. Procalcitonin is an excellent sepsis marker with a high positive- and negative-predictive value in patients with WBC count > 1.0 x 10(9)/l, but it does not work satisfactorily below this leucocyte count.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Immunosuppression Therapy; Leukocyte Count; Leukopenia; Predictive Value of Tests; Protein Precursors; Sepsis; Shock, Septic; Statistics, Nonparametric

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis; Shock, Septic

To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II).. Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period.. A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms.. PCT values were highest in patients with septic shock (12.89+/-4.39 ng/ml;P<0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91+/-3.87 ng/ml vs 0.53+/-2.9 ng/ml;P<0.001, and 0.41+/-3.04 ng/ml;P<0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26+/-1.62, 16.09+/-2.06, and 17.42+/-1.72 points, respectively), but was significantly higher in patients with septic shock (29.27+/-1.35,P<0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock.. In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.

Topics: Adult; Aged; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Diagnosis, Differential; Early Diagnosis; Female; Germany; Humans; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Shock, Septic; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome

To evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection in ICU medical and surgical patients.. A 10-bed medical surgical unit.. PCT, C-reactive protein (CRP), interleukin 6 (IL-6) dosages were sampled in four groups of patients: septic shock patients (SS group), shock without infection (NSS group), patients with systemic inflammatory response syndrome related to a proven bacterial infection (infect. group) and ICU patients without shock and without bacterial infection (control group).. Sixty patients were studied (SS group:n=16, NSS group,n=18, infect. group,n=16, control group,n=10). The PCT level was higher in patients with proven bacterial infection (72+/-153 ng/ml vs 2.9+/-10 ng/ml,p=0.0003). In patients with shock, PCT was higher when bacterial infection was diagnosed (89 ng/ml+/-154 vs 4.6 ng/ml+/-12,p=0.0004). Moreover, PCT was correlated with severity (SAPS:p=0.00005, appearance of shock:p=0.0006) and outcome (dead: 71.3 g/ml, alive: 24.0 g/ml,p=0.006). CRP was correlated with bacterial infection (p<10(-5)) but neither with SAPS nor with day 28 mortality. IL-6 was correlated with neither infection nor day 28 mortality but was correlated with SAPS. Temperature and white blood cell count were unable to distinguish shocked patients with or without infection. Finally, when CRP and PCT levels were introduced simultaneously in a stepwise logistic regression model, PCT remained the unique marker of infection in patients with shock (PCT> or =5 ng/ml, OR: 6.2, 95% CI: 1.1-37,p=0.04).. The increase of PCT is related to the appearance and severity of bacterial infection in ICU patients. Thus, PCT might be an interesting parameter for the diagnosis of bacterial infections in ICU patients.

Topics: Acute Disease; Adult; Aged; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Critical Illness; Female; France; Glycoproteins; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index; Shock, Septic

Disseminated herpes simplex virus infection is a potentially fatal condition which may be difficult to differentiate from bacterial sepsis. We report the case of a neonate with overwhelming herpes simplex (type 2) viraemia who presented with 'septic shock'.. A low procalcitonin level (1.6 ng/ml), inconsistent with bacteraemia, suggests an alternative aetiology and may strengthen the case for antiviral therapy.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Fatal Outcome; Female; Herpes Genitalis; Humans; Infant, Newborn; Protein Precursors; Sepsis; Shock, Septic

Procalcitonin (PCT), a marker of bacterial sepsis, may also act as a mediator of the inflammatory response to infection, and thus influence outcome.. To investigate the relationship between PCT, interleukin (IL)-10, tumor necrosis factor (TNF), organ failure, and mortality in pediatric septic shock.. Prospective observational study.. A 16-bed pediatric intensive care unit of a university hospital.. A total of 75 children with septic shock having a median age of 43.1 months (range, 0.1-192 months). Children who had received antibiotics for >24 hrs were excluded. A total of 37 patients (49%) had meningococcal disease, and 72 patients (96%) required mechanical ventilation.. The pediatric risk of mortality (PRISM) score, multiple organ system failure (MOSF) score, duration of ventilation, length of ICU stay, and outcome were recorded. PCT, IL-10, and TNF were measured at admission to the intensive care unit. Sequential PCT levels were available at 0 hrs and 24 hrs in 39 patients (52%).. Observed mortality was 21/75 (28%). Data are median (range). The admission PCT (p = .0002) and TNF levels (p = .0001) were higher in children with higher MOSF scores. In survivors and nonsurvivors, the admission PCT was 82 ng/mL vs. 273 ng/mL (p = .03), IL-10 was 62 pg/mL vs. 534 pg/mL (p = .03), and TNF was 76 pg/mL vs. 480 pg/mL (p = .001), respectively. Area under the mortality receiver operating characteristic curve was 0.73 for PCT, 0.67 for IL-10, and 0.76 for TNF, compared with 0.83 for the PRISM score. Of 39 children, 16 (41%) with sequential PCT measurements showed no fall in PCT after 24 hrs treatment. These children had higher admission levels of IL-10 (p = .03), and TNF (p = .03) compared with children who demonstrated a subsequent fall in PCT. Although the former did not have a higher median PRISM (p = .28) or MOSF score (p = .19), observed mortality was 44% (7 of 16) compared with 9% (2 of 23) (p = .02).. The admission PCT, like TNF and IL-10, is related to the severity of organ failure and mortality in children with septic shock. A fall in PCT after 24 hrs of treatment may have favorable prognostic significance.

Topics: Adolescent; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Humans; Infant; Intensive Care Units, Pediatric; Interleukin-10; Length of Stay; Multiple Organ Failure; Prognosis; Prospective Studies; Protein Precursors; Respiration, Artificial; ROC Curve; Severity of Illness Index; Shock, Septic; Tumor Necrosis Factor-alpha

To determine the value of procalcitonin (PCT) as a marker of postoperative infection after cardiac surgery.. A prospective single institution three phase study.. University cardiac surgical intensive care unit (31 beds).. Phase 1: To determine the normal perioperative kinetics of PCT, 20 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass were included. Phase 2: To determine whether PCT may be useful for diagnosis of postoperative infection, 97 consecutive patients with suspected infection were included. Phase 3: To determine the ability of PCT to differentiate patients with septic shock from those with cardiogenic shock, 26 patients with postoperative circulatory failure were compared.. Phase 1: Serum samples were drawn for PCT determination after induction of anesthesia (baseline), at the end of surgery, and daily until postoperative day (POD) 8. Baseline serum PCT concentration was 0.17 +/- 0.08 ng/mL (mean +/- SD). Serum PCT increased after cardiac surgery with a peak on POD 1 (1.08 +/- 1.36). Serum PCT returned to normal range on POD 3 and remained stable thereafter. Phase 2: In patients with suspected infection, serum PCT was measured at the same time of C-reactive protein (CRP) and bacteriologic samples. Among the 97 included patients, 54 were infected with pneumonia (n = 17), bacteremia (n = 16), mediastinitis (n = 9), or septic shock (n = 12). In the 43 remaining patients, infection was excluded by microbiological examinations. In noninfected patients, serum PCT concentration was 0.41 +/- 0.36 ng/mL (range, 0.08-1.67 ng/mL). Serum PCT concentration was markedly higher in patients with septic shock (96.98 +/- 119.61 ng/mL). Moderate increase in serum PCT concentration occurred during pneumonia (4.85 +/-3.31 ng/mL) and bacteremia (3.57 +/- 2.98 ng/mL). Serum PCT concentration remained low during mediastinitis (0.80 +/- 0.58 ng/mL). Five patients with mediastinitis, two patients with bacteremia, and one patient with pneumonia had serum PCT concentrations of <1 ng/mL. These eight patients were administered antibiotics previously and serum PCT was measured during a therapeutic antibiotic window. For prediction of infection by PCT, the best cutoff value was 1 ng/mL, with sensitivity 85%, specificity 95%, positive predictive value 96%, and negative predictive value 84%. Serum CRP was high in all patients without intergroup difference. For prediction of infection by CRP, a value of 50 mg/L was sensitive (84%) but poorly specific (40%). Comparing the area under the receiver operating characteristic curves, PCT was better than CRP for diagnosis of postoperative sepsis (0.82 for PCT vs. 0.68 for CRP). Phase 3: Serum PCT concentration was significantly higher in patients with septic shock than in those with cardiogenic shock (96.98 +/- 119.61 ng/mL vs. 11.30 +/- 12.3 ng/mL). For discrimination between septic and cardiogenic shock, the best cutoff value was 10 ng/mL, with sensitivity of 100% and specificity of 62%.. Cardiac surgery with cardiopulmonary bypass influences serum PCT concentration with a peak on POD 1. In the presence of fever, PCT is a reliable marker for diagnosis of infection after cardiac surgery, except in patients who previously received antibiotics. PCT was more relevant than CRP for diagnosis of postoperative infection. During a postoperative circulatory failure, a serum PCT concentration >10 ng/mL is highly indicative of a septic shock.

Topics: Adult; Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Diagnosis, Differential; Female; Heart Diseases; Heart Failure; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Shock, Cardiogenic; Shock, Septic; Surgical Wound Infection

The elimination of procalcitonin and the course of plasma concentrations during continuous veno-venous haemodiafiltration were measured in patients with sepsis or multiple organ dysfunction syndrome, because these patients are a main target group for the measurement of procalcitonin and often require renal replacement therapy. Procalcitonin was measured in the prefilter plasma and the filtrate at 5 min, 15 min and 1, 2, 4, 6, 12, 24 h after set-up of continuous veno-venous haemodiafiltration. In a prospective study, 19 patients with plasma levels of procalcitonin > 3 ng mL-1 and acute oliguric renal failure treated with continuous veno-venous haemodiafiltration using a polysulphone membrane, were evaluated for the study of clearance. Twenty-one control patients (procalcitonin < 2 ng mL-1) were studied to determine whether filtration itself induced a procalcitonin response. No interventions were required. In patients with low procalcitonin concentrations (procalcitonin < 2 ng mL-1) continuous veno-venous haemodiafiltration did not cause a rise in procalcitonin. In patients with increased procalcitonin plasma concentrations (> 3 ng mL-1), the protein was removed through the polysulphone membrane, with a final clearance of 4 mL min-1 after the initial adsorption period (clearance 0.4-0.9 mL min-1 during the first hour of continuous veno-venous haemodiafiltration). Thus, on the average, approximately 10% of plasma concentrations were measurable in the filtrate ultimately. However, procalcitonin plasma levels were not significantly altered during continuous veno-venous haemodiafiltration (86% of the initial concentration after 24 h). Although procalcitonin is removed from the plasma during continuous veno-venous haemodiafiltration in measurable amounts plasma procalcitonin concentrations did not change significantly during haemodiafiltration. Procalcitonin thus can also be used as a diagnostic parameter in patients undergoing continuous veno-venous haemodiafiltration.

Topics: Acute Kidney Injury; Adsorption; Aged; Biocompatible Materials; Calcitonin; Calcitonin Gene-Related Peptide; Female; Follow-Up Studies; Glycoproteins; Hemodiafiltration; Humans; Male; Membranes, Artificial; Middle Aged; Multiple Organ Failure; Polymers; Prospective Studies; Protein Precursors; Renal Replacement Therapy; Sepsis; Shock, Septic; Statistics, Nonparametric; Sulfones

Procalcitonin (PCT) has been described as an early, discriminating marker of bacteria-associated sepsis in patients. However, little is known of its source and actions, in part because no appropriate animal models have been available. We tested the hypothesis that plasma PCT increases during various pathophysiological conditions, such as hemorrhagic shock and sepsis, which differ with regard to the degree of associated endotoxemia. We further hypothesized that in sepsis, PCT would be significantly different in survivors vs. nonsurvivors.. Prospective, blinded analysis of previously collected plasma of experimental animals.. Independent nonprofit research laboratory in a trauma hospital and a contract research institute.. A total of 22 male baboons (17.5-31 kg).. Hemorrhagic-traumatic shock was induced by hemorrhage for up to 3 hrs, reperfusion with shed blood and infusion of cobra venom factor (n = 7). By using a similar experimental setup, severe hyperdynamic sepsis was induced (n = 15) by intravenous infusion of live Escherichia coli (2 x 10(9) colony-forming units/kg) over 2 hrs, followed by antibiotic therapy (gentamicin 4 mg/kg twice a day).. Plasma PCT at baseline was barely detectable, but levels increased significantly (p < .05) to 2+/-1.8 pg/mL 2 hrs after the start of reperfusion in the shock group, and to 987+/-230 pg/mL at 4 hrs after E. coli in the sepsis group. Levels were maximal between 6 and 32 hrs and had returned nearly to baseline levels at 72 hrs. Interleukin-6 levels paralleled the course of PCT measurements, whereas a significant increase in neopterin was seen at 24 hrs. PCT levels were approximately three times higher in the sepsis group than in the shock group, corresponding to endotoxin levels (at the end of hemorrhage, 286+/-144 pg/mL vs. 3576+/-979 pg/mL at the end of E. coli infusion; p = .003). PCT levels were significantly different at 24 hrs between survivors (2360+/-620 pg/mL) and nonsurvivors (4776+/-563 pg/mL) in the sepsis group (p = .032), as were interleukin-6 (1562+/-267 vs. 4903+/-608 pg/mL; p = .01) and neopterin/creatinine ratio (0.400+/-0.038 vs. 0.508+/-0.037; p = .032).. PCT is detectable in the baboon as in humans, both in hemorrhagic shock and sepsis. PCT levels are significantly higher in sepsis than in hemorrhage, a finding that is probably related to the differences in endotoxin. The baboon can be used for the study of PCT kinetics in both models; PCT kinetics are clearly different from other markers of sepsis, either IL-6 or neopterin, in both models. There are significant differences between survivors and nonsurvivors in the sepsis model.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Disease Models, Animal; Escherichia coli Infections; Interleukin-6; Male; Neopterin; Papio; Protein Precursors; Shock, Hemorrhagic; Shock, Septic; Survival Rate; Systemic Inflammatory Response Syndrome; Wounds and Injuries

Procalcitonin (PCT) was shown to be related to the severity of bacterial infection and is recommended as a new parameter of inflammation and infection. To evaluate the prognostic value in septic shock, PCT levels were repeatedly determined and compared with tumour necrosis factor-alpha (TNF-alpha)- and interleukin (IL)-6 bioactivity as well as with C-reactive protein (CRP) serum levels.. Twenty-four surgical patients with septic shock were included. Eight patients died within the study period of 14 days.. Serum levels of TNF-(WEHI 164) and IL-6 (B13-29 subclone 9) bioactivity, CRP and PCT were determined on days 1, 3, 5, 7, 10 and 14 following diagnosis of septic shock.. Survivors and non-survivors were comparable in terms of age and severity of sepsis characterized by the APACHE II score and multiple-organ-failure score. Predominant causes of sepsis were peritonitis and necrotiszing pancreatitis. TNF levels increased in non-survivors with no significant difference to survivors. IL-6 bioactivity was increased on day 1 (P = 0.06) and remained elevated in non-survivors, in whom it was significant on day 7 (P<0.05). CRP was constantly elevated with no difference between the groups. In nonsurvivors PCT remained increased, while the course of survivors was characterized by decreased values which were significantly lower (P<0.05) at every time point compared with those patients who died. A significant correlation could be found on day 1 (P<0.05) and at the end of the observation period (P<0.01) when comparing PCT levels with the multiple-organ-failure score.. PCT seems to be a more reliable prognostic parameter in septic shock than IL-6, while TNF and CRP did not show any difference between survivors and non-survivors. These data indicate that PCT may represent a valuable parameter not only in the diagnosis of sepsis but also in the clinical course of the disease.

Topics: APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycoproteins; Humans; Interleukin-6; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Peritonitis; Prognosis; Protein Precursors; Severity of Illness Index; Shock, Septic; Tumor Necrosis Factor-alpha

Procalcitonin has been advocated as a marker of bacterial infection.. To evaluate diagnostic markers of infection in critically ill children, comparing procalcitonin with C reactive protein and leucocyte count in a paediatric intensive care unit (PICU).. Procalcitonin, C reactive protein, and leucocyte count were measured in 175 children, median age 16 months, on admission to the PICU. Patients were classified as: non-infected controls (43); viral infection (14); localised bacterial infection without shock (25); bacterial meningitis/encephalitis (10); or septic shock (77). Six children with "presumed septic shock" (without sufficient evidence of infection) were analysed separately. Optimum sensitivity, specificity, predictive values, and area under the receiver operating characteristic (ROC) curve were evaluated.. Admission procalcitonin was significantly higher in children with septic shock (median 94.6; range 3.3-759.8 ng/ml), compared with localised bacterial infection (2.9; 0-24.3 ng/ml), viral infection (0.8; 0-4.4 ng/ml), and non-infected controls (0; 0-4.9 ng/ml). Children with bacterial meningitis had a median procalcitonin of 25.5 (7.2-118.4 ng/ml). Area under the ROC curve was 0.96 for procalcitonin, 0.83 for C reactive protein, and 0.51 for leucocyte count. Cut off concentrations for optimum prediction of septic shock were: procalcitonin > 20 ng/ml and C reactive protein > 50 mg/litre. A procalcitonin concentration > 2 ng/ml identified all patients with bacterial meningitis or septic shock.. In critically ill children the admission procalcitonin concentration is a better diagnostic marker of infection than C reactive protein or leucocyte count. A procalcitonin concentration of 2 ng/ml might be useful in differentiating severe bacterial disease in infants and children.

Topics: Adolescent; Age Factors; Analysis of Variance; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Care; Glycoproteins; Humans; Infant; Infant, Newborn; Leukocyte Count; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve; Shock, Septic

Exposure to bacterial endotoxin, perhaps due to bowel congestion or ischaemia and altered gut permeability, may result in immune activation that is characteristic for patients with severe heart failure. It is known that blood procalcitonin rises in response to bacterial endotoxin exposure.. We measured procalcitonin in a group of 29 patients with acute cardiogenic shock and no sign of infection (all without bacteraemia) and 26 with septic shock. Blood was analysed for procalcitonin, interleukin-6, tumour necrosis factor-alpha (TNF-alpha), c-reactive protein (CRP) and neopterin. Patients were managed conventionally in an intensive care unit with no further experimental procedures.. Three cardiogenic (10%) and seven septic shock patients (27%) survived. Most patients with acute heart failure surviving 12 h or more (18 of 20) developed a pyrexia (738.0 degrees C) of unknown origin in the absence of positive cultures, with a rise in procalcitonin (1.4+/-0.8 to 48.0+/-16.2 ng/ml, P<0.001), CRP (76.5+/-16.4 to 154.7+/-22.9 mg/l, P<0.001) and neopterin (20.7+/-3.5 to 41.2+/-6.7 nmol/l, P<0.001). Patients with septic shock had higher initial levels of cytokines, and higher peak levels. Those with heart failure surviving (n=3) and those dying in the first 12 h (n=9) had no rise in cytokine levels. The patients with high procalcitonin had a higher temperature (38.9+/-0.3 vs. 37.3+/-0.23 degrees C, P<0.05), TNF-alpha (43.95+/-9.64 vs. 16.43+/-4.33 pg/ml; P<0.005) and CRP (146.1+/-18.4 vs. 68.2+/-39.6 mg/ml, P<0.005). Peak procalcitonin levels correlated with peak temperature (r=0.74, P<0.001).. Cardiogenic shock causes a pyrexia of unknown origin in patients surviving for 12 h and that is associated with a rise in procalcitonin levels. This lends support to the hypothesis that patients with cardiogenic shock may be being exposed to bacterial endotoxin at a time when bowel wall congestion and or ischaemia is likely to be present.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Translocation; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Endotoxins; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Protein Precursors; Shock, Cardiogenic; Shock, Septic; Survival Analysis

To determine and compare the respective concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble TNF receptors, nitrite/nitrate (NO2-/NO3-), and procalcitonin in the plasma of patients with septic shock, cardiogenic shock, and bacterial pneumonia without shock; and to assess the predictive value of these mediators in defining patients with septic shock.. Cohort study, comparing normal volunteers (controls) and patients with septic shock, cardiogenic shock, and bacterial pneumonia.. A collaborative study among an intensive care unit, an emergency room, and three research laboratories.. Mediators were measured at various times in 15 patients with septic shock (during the shock phase and during the recovery phase), in seven patients with cardiogenic shock during the shock phase, and in seven patients with severe bacterial pneumonia on day 1 of admission.. Blood samples were collected at various times during the course of the disease.. TNF-alpha values were highest in the acute phase of septic shock (53 to 131 pg/mL during septic shock), while patients with bacterial pneumonia had intermediate concentrations (32 pg/mL). TNF-alpha concentrations were normal in patients with cardiogenic shock. IL-6 concentrations were highest in patients with acute septic shock (85 to 385 pg/mL). However, in contrast to TNF-alpha concentrations, IL-6 concentrations were normal in patients with bacterial pneumonia and increased in patients with cardiogenic shock (78 pg/mL). Soluble TNF receptors were increased in all three groups vs. controls, with the highest increase in patients with septic shock. NO2-/NO3- concentrations were highest (72 to 140 mM) in patients with septic shock, and were < 40 mM in the other groups of patients. Procalcitonin concentrations were only markedly increased in patients with septic shock (72 to 135 ng/mL, compared with approximately 1 ng/mL in the three other groups). The best predictive value for septic shock was found to be the measurements of NO2-/NO3- and procalcitonin concentrations.. These observations showed that increase of proinflammatory cytokines was a consequence of inflammation, not of shock. In this study comparing various shock and infectious states, measurements of NO2-/NO3- concentration and procalcitonin concentration represented the most suitable tests for defining patients with septic shock.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Cytokines; Diagnosis, Differential; Female; Humans; Interleukin-6; Male; Middle Aged; Nitrates; Nitrites; Pneumonia, Bacterial; Predictive Value of Tests; Protein Precursors; Receptors, Tumor Necrosis Factor; Shock, Cardiogenic; Shock, Septic; Tumor Necrosis Factor-alpha

Topics: Addison Disease; Adolescent; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Protein Precursors; Shock, Septic

Increased serum concentration of procalcitonin (PCT) in limited number of paediatric patients with acute severe bacterial infections has been described previously. In a prospective study in 337 hospitalised adult patients fulfilling the SIRS-criteria, serum PCT was determined on admission and up to 9 days thereafter. Patients with microbiologically documented infection showed peak values of 30 ng/ml at day 3, which rapidly decreased to normal levels. Patients without sepsis revealed baseline values (0.1 ng/ml or lower). The validity criteria were calculated for several breakpoints of PCT. We detected an interval from 0.1 to 0.5 ng/ml under which a severe microbial infection is unlikely (sensitivity 91%, specificity 25%, positive predictive value 39%, negative predictive value 86%). An infection is most likely above 0.5 ng/ml (sensitivity 60%, specificity 79%, positive predictive value 61%, negative predictive value 78%). Between these two points an infection can neither be confirmed nor excluded. The excellent specificity and negative predictive value at a cut-off point of 0.5 ng/ml suggests that this test might be a useful parameter in the management of infectious diseases.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Predictive Value of Tests; Prospective Studies; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Sepsis; Shock, Septic