calca-protein--human and Critical-Illness

Procalcitonin (PCT)-based antibiotic management algorithms for critically ill patients have been described in the literature. An evaluation of the available evidence demonstrates that studies have utilised PCT in various clinical scenarios: for the initiation of antimicrobials; for cessation or de-escalation of antimicrobials; or for the combination of both strategies. Current PCT reviews and meta-analyses have combined studies from all different clinical scenarios. However, there may be significant variations in algorithm compliance and clinical outcomes associated with the use of PCT in these different strategies. As such, the current review focused on separating out the studies utilising PCT in the critically ill population for different treatment strategies. Based on this review, we would recommend that PCT should not be used as the sole deciding factor for the initiation of antimicrobials. As such, PCT should not be obtained in patients who do not exhibit evidence of infection. In patients who do have signs of infection and antimicrobials have been initiated, a strategy that utilises PCT for the discontinuation or de-escalation of antimicrobials is likely to decrease the duration of treatment without adversely affecting outcome.

Topics: Algorithms; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Decision Support Techniques; Humans; Protein Precursors

This meta-analysis was performed to determine the accuracy of procalcitonin (PCT) in predicting mortality in pneumonia patients with different pathogenic features and disease severities. A systematic search of English-language articles was performed using PubMed, Embase, Web of Knowledge and the Cochrane Library to identify studies. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. The Q-test and I(2) index were used to test heterogeneity. A total of 21 studies comprising 6007 patients were included. An elevated PCT level was a risk factor for death from community-acquired pneumonia (CAP) (risk ratio (RR) 4.38, 95% confidence interval (CI) 2.98-6.43), particularly in patients with a low CURB-65 score. The commonly used cut-off, 0.5 ng/mL, had low sensitivity (SEN) and was not able to identify patients at high risk of dying. Furthermore, the PCT assay with functional SEN <0.1 ng/mL was necessary to predict mortality in CAP in the clinic. For critically ill patients, an elevated PCT level was associated with an increased risk of mortality (RR 4.18, 95% CI: 3.19-5.48). The prognostic performance was nearly equal between patients with ventilator-associated pneumonia (VAP) and patients with CAP.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Critical Illness; Glycoproteins; Humans; Pneumonia; Pneumonia, Ventilator-Associated; Predictive Value of Tests; Prognosis; Protein Precursors; Risk Assessment

Effective antimicrobial stewardship is an increasingly important concern for healthcare providers globally. Antibiotics are frequently prescribed for patients who develop sepsis in the intensive care unit and traditionally courses are prolonged, with uncertain benefit and probable harm. There is little evidence to support many guidelines recommending between 10 and 14 days, and a number of studies suggest substantially shorter courses of less than 7 days may suffice. Safely reducing course length is likely to depend on a number of preconditions, including thorough eradication of any septic foci; optimization of serum antibiotic concentrations, particularly when there is physiological derangement; and use of novel biomarkers such as procalcitonin. The critical care environment is well suited to this aim as patients are closely monitored. With these measures in place, it is reasonable to believe short antibiotic courses can safely be used for the majority of intensive care infections.

Topics: Anti-Bacterial Agents; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Drug Administration Schedule; Enterobacteriaceae; Haemophilus influenzae; Humans; Intensive Care Units; Microbial Sensitivity Tests; Protein Precursors; Pseudomonas; Sepsis; Staphylococcus aureus; Streptococcus pneumoniae; Time Factors

We reviewed the use of the levels of C-reactive protein, lactate and procalcitonin and/or the Sequential Organ Failure Assessment score to determine their diagnostic accuracy for predicting surgical complications in critically ill general post-surgery patients. Included were all studies published in PubMed from inception to July 2013 that met the following inclusion criteria: evaluation of the above parameters, describing their diagnostic accuracy and the risk stratification for surgical complications in surgical patients admitted to an intensive care unit. No difference in the Sequential Organ Failure Assessment scores was seen between patients with or without complications. The D-lactate levels were significantly higher in those who developed colonic ischemic complications after a ruptured abdominal aortic aneurysm. After gastro-intestinal surgery, contradictory data were reported, with both positive and negative use of C-reactive protein and procalcitonin in the diagnosis of septic complications. However, in trauma patients, the C-reactive protein levels may help to discriminate between those with and without infectious causes. We conclude that the Sequential Organ Failure Assessment score, lactate concentration and C-reactive protein level have no significant predictive value for early postoperative complications in critically ill post-surgery patients. However, procalcitonin seems to be a useful parameter for diagnosing complications in specific patient populations after surgery and/or after trauma.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Forecasting; Humans; Intensive Care Units; Lactic Acid; Organ Dysfunction Scores; Postoperative Complications; Protein Precursors; PubMed; Sensitivity and Specificity

Critically ill patients are frequently at risk of sepsis or inflammatory conditions. Procalcitonin (PCT) is a biomarker for critically ill patients to differentiate sepsis from non-infectious triggers of the systemic inflammatory response syndrome. It has been recently shown that PCT is a valuable tool to guide antibiotic treatment in patients with bacteria infections. However, PCT is also less than a universal and perfect biomarker, and its physiologic role remains unknown. An increase in PCT is associated not only with localized bacterial infection, but also with non-infectious disease or other microbial infections. Numerous studies have suggested that use of PCT would reduce patients' exposure to antibiotics; however, the use of PCT-guided management of antibiotics strategy needs further study to validate their safety in daily practice in ICU settings. Data supporting this concept from randomized trials are still required. Future studies should focus on PCT kinetics. On the other hand, the need for biologic role of PCT shall be highlighted. Immunoneutralization of PCT will likely be a therapeutic approach for human sepsis only if its physiologic effects are elaborated. The aim of this review is to summarize and discuss the current evidence for PCT in a series of clinical settings.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Protein Precursors; Sepsis

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

Procalcitonin (PCT) is helpful for diagnosing bacterial infections. The diagnostic utility of PCT has not been examined thoroughly in critically ill patients with suspected H1N1 influenza.. Clinical characteristics and PCT were prospectively assessed in 46 patients with pneumonia admitted to medical ICUs during the 2009 and 2010 influenza seasons. An individual patient data meta-analysis was performed by combining our data with data from five other studies on the diagnostic utility of PCT in ICU patients with suspected 2009 pandemic influenza A(H1N1) virus infection identified by performing a systematic literature search.. PCT levels, measured within 24 hours of ICU admission, were significantly elevated in patients with bacterial pneumonia (isolated or coinfection with H1N1; n = 77) (median = 6.2 μg/L, interquartile range (IQR) = 0.9 to 20) than in patients with isolated H1N1 influenza pneumonia (n = 84; median = 0.56 μg/L, IQR = 0.18 to 3.33). The area under the curve of the receiver operating characteristic curve of PCT was 0.72 (95% confidence interval (CI) = 0.64 to 0.80; P < 0.0001) for diagnosis of bacterial pneumonia, but increased to 0.76 (95% CI = 0.68 to 0.85; P < 0.0001) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. PCT at a cut-off of 0.5 μg/L had a sensitivity (95% CI) and a negative predictive value of 80.5% (69.9 to 88.7) and 73.2% (59.7 to 84.2) for diagnosis of bacterial pneumonia, respectively, which increased to 85.5% (73.3 to 93.5) and 82.2% (68.0 to 92.0) in patients without hospital acquired pneumonia or immune-compromising disorder.. In critically ill patients with pneumonia during the influenza season, PCT is a reasonably accurate marker for detection of bacterial pneumonia, particularly in patients with community-acquired disease and without immune-compromising disorders, but it might not be sufficient as a stand-alone marker for withholding antibiotic treatment.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Critical Illness; Cross Infection; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Pandemics; Pneumonia, Bacterial; Prospective Studies; Protein Precursors; Retrospective Studies

Persistent organ failure and infected pancreatic necrosis are major determinants of mortality in acute pancreatitis, but there is a gap in the literature assessing the best available predictors of these two determinants. The purpose of this review was to investigate the utility of predictors of persistent organ failure and infected pancreatic necrosis in patients with acute pancreatitis, both alone and in combination.. We performed a systematic search of the literature in 3 databases for prospective studies evaluating predictors of persistent organ failure, infected pancreatic necrosis, or both, with strict eligibility criteria.. The best predictors of persistent organ failure were the Japanese Severity Score and Bedside Index of Severity in Acute Pancreatitis when the evaluation was performed within 48h of admission, and blood urea nitrogen and Japanese Severity Score after 48h of admission. Systemic Inflammation Response Syndrome was a poor predictor of persistent organ failure. The best predictor of infected pancreatic necrosis was procalcitonin.. Based on the best available data, it is justifiable to use blood urea nitrogen for prediction of persistent organ failure after 48h of admission and procalcitonin for prediction of infected pancreatic necrosis in patients with confirmed pancreatic necrosis. There is no predictor of persistent organ failure that can be justifiably used in clinical practice within 48h of admission.

Topics: Acute Disease; Blood Urea Nitrogen; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Disease Progression; Humans; Multiple Organ Failure; Necrosis; Pancreas; Pancreatitis, Acute Necrotizing; Predictive Value of Tests; Protein Precursors; Severity of Illness Index; Systemic Inflammatory Response Syndrome

Sepsis is one of the leading causes of death in the critically ill. Early diagnosis is important to avoid delay in instituting appropriate treatment. However, diagnosis can be delayed because of difficulty in interpreting clinical features. Sepsis biomarkers can aid early diagnosis. This article reviews the application of readily available biomarkers for diagnosis of sepsis, for predicting prognosis, and for antibiotic stewardship. 178 biomarkers are described in the literature--ranging from specimen cultures, which lack sensitivity and specificity for early diagnosis of sepsis, to biomarkers such as C-reactive protein, procalcitonin, and genetic biomarkers, which have their own limitations. Future research will mainly focus on use of more than one biomarker, but the main problem in sepsis biomarker research seems to be a lack of a recommended biomarker.

Topics: Antigens, Bacterial; Biomarkers; Blood Cell Count; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Genome; Humans; Predictive Value of Tests; Prognosis; Protein Precursors; Proteomics; Receptors, Immunologic; Sepsis; Treatment Outcome

Procalcitonin is a promising marker for identification of bacterial infections. We assessed the accuracy and clinical value of procalcitonin for diagnosis of sepsis in critically ill patients.. We searched Medline, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, and Science Direct, from inception to Feb 21, 2012, and reference lists of identified primary studies. We included articles written in English, German, or French that investigated procalcitonin for differentiation of septic patients--those with sepsis, severe sepsis, or septic shock--from those with a systemic inflammatory response syndrome of non-infectious origin. Studies of healthy people, patients without probable infection, and children younger than 28 days were excluded. Two independent investigators extracted patient and study characteristics; discrepancies were resolved by consensus. We calculated individual and pooled sensitivities and specificities. We used I(2) to test heterogeneity and investigated the source of heterogeneity by metaregression.. Our search returned 3487 reports, of which 30 fulfilled the inclusion criteria, accounting for 3244 patients. Bivariate analysis yielded a mean sensitivity of 0 · 77 (95% CI 0 · 72-0 · 81) and specificity of 0 · 79 (95% CI 0 · 74-0 · 84). The area under the receiver operating characteristic curve was 0 · 85 (95% CI 0 · 81-0 · 88). The studies had substantial heterogeneity (I(2)=96%, 95% CI 94-99). None of the subgroups investigated--population, admission category, assay used, severity of disease, and description and masking of the reference standard--could account for the heterogeneity.. Procalcitonin is a helpful biomarker for early diagnosis of sepsis in critically ill patients. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, physical examination, and microbiological assessment.. Ministry of Education and Research, the Deutsche Forschungsgemeinschaft, Thuringian Ministry for Education, Science and Culture, the Thuringian Foundation for Technology, Innovation and Research, and the German Sepsis Society.

Topics: Age Factors; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Databases, Factual; Humans; Prevalence; Protein Precursors; Regression Analysis; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

We sought to perform a systematic review and meta-analysis of procalcitonin(PCT)-guided antibiotic therapy algorithms for critically ill adult patients.. We performed a search in PubMed and in the Cochrane Central Register of Controlled Trials. Seven evaluable randomised clinical trials (RCTs) were identified and analysed. Primary outcomes included the duration of antibiotic therapy for the first episode of infection and 28-day mortality. Secondary outcomes included length of ICU stay, length of hospitalisation, antibiotic-free days within the first 28 days of hospitalisation, recurrences, and superinfections.. Data on the duration of antibiotic therapy for the first episode of infection were provided in five out of seven included RCTs, while data on 28-day mortality were provided in all of the included RCTs. Duration of antibiotic therapy for the first episode of infection was reduced in favour of PCT-guided treatment [pooled weighted mean difference (WMD) = -3.15 days, random effects model, 95 % confidence interval (CI) -4.36 to -1.95, P < 0.001]. There was no difference in 28-day mortality between the compared arms [fixed effect model (FEM), odds ratio = 0.96, 95 % CI 0.79-1.15, P = 0.63). Antibiotic-free days were increased within the first 28 days of hospitalisation in favour of the PCT-guided treatment arm (pooled WMD = 3.08 days, FEM, 95 % CI 2.06-4.10, P < 0.001). No difference was found regarding the remaining outcomes. Sensitivity analyses including studies of higher quality and studies using the TRACE method to measure PCT yielded similar results.. Procalcitonin-guided antibiotic therapy algorithms could help in reducing the duration of antimicrobial administration without having a negative impact on survival.

Topics: Algorithms; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Protein Precursors

Procalcitonin (PCT) has emerged as the most specific biomarker for bacterial infection. As clinicians become more familiar with its use, a multitude of observational studies have reported on its diagnostic potential in distinct types of infections and various clinical situations, such as in neutropenia or in the postoperative period. In the Intensive Care Unit setting, however, the prognostic value of a single PCT measurement at the time of admission on a patient with sepsis is suboptimal. Especially in cases of community-acquired pneumonia, cardiovascular biomarkers, such as mid-regional proadrenomedullin, seem to carry stronger prognostic potential than PCT. Nevertheless, the study of PCT kinetics may still be of use as a risk assessment tool for the general population of critically ill patients with sepsis syndrome. The most recent significant development in the field of PCT monitoring, is the publication of several randomized controlled trials that investigated its use as a decision making tool for the initiation and/or the duration of antibiotic treatment. Currently, the available evidence suggests that the incorporation of PCT measurements to assist with the duration of antibiotic stewardship programs may decrease antibiotic use without compromising clinical outcomes. Nevertheless, this strategy still needs further validation in large prospective studies.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Humans; Prognosis; Protein Precursors; Sepsis; Treatment Outcome

The purpose of this systematic review was to assess the evidence for use of routine procalcitonin testing to diagnose the presence of sepsis in the burn patient. The electronic databases MEDLINE, Cochrane, CINAHL, ProQuest, and SCOPUS were searched for relevant studies using the MeSH terms burn, infection, procalcitonin, and meta-analysis. The focus of the review was the adult burn population, but other relevant studies of critically ill patients were included as data specific to the patient with burns are limited. Studies were compiled in tabular form and critically appraised for quality and level of evidence. Four meta-analyses, one review of the literature, one randomized controlled trial, nine prospective observational, and three retrospective studies were retrieved. Six of these studies were specific to the burn population, with one specific to burned children. Only one meta-analysis, one adult burn and one pediatric burn study reported no benefit of procalcitonin testing to improve diagnosis of sepsis or differentiate sepsis from non-infectious systemic inflammatory response. The collective findings of the included studies demonstrated benefit of incorporating procalcitonin assay into clinical sepsis determination. Evaluation of the burn specific studies is limited by the use of guidelines to define sepsis and inconsistent results from the burn studies. Utility of the procalcitonin assay is limited due to the lack of availability of rapid, inexpensive tests. However, it appears procalcitonin assay is a safe and beneficial addition to the clinical diagnosis of sepsis in the burn intensive care unit.

Topics: Adult; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Protein Precursors; Sepsis

Sepsis is a leading cause of mortality in critically ill patients. Delay in diagnosis and initiation of antibiotics have been shown to increase mortality in this cohort. However, differentiating sepsis from non-infectious triggers of the systemic inflammatory response syndrome (SIRS) is difficult, especially in critically ill patients who may have SIRS for other reasons. It is this conundrum that predominantly drives broad-spectrum antimicrobial use and the associated evolution of antibiotic resistance in critical care environments. It is perhaps unsurprising, therefore, that the search for a highly accurate biomarker of sepsis has become one of the holy grails of medicine. Procalcitonin (PCT) has emerged as the most studied and promising sepsis biomarker. For diagnostic and prognostic purposes in critical care, PCT is an advance on C-reactive protein and other traditional markers of sepsis, but is not accurate enough for clinicians to dispense with clinical judgement. There is stronger evidence, however, that measurement of PCT has a role in reducing the antibiotic exposure of critical care patients. For units intending to incorporate PCT assays into routine clinical practice, the cost-effectiveness of this is likely to depend on the pre-implementation length of an average antibiotic course and the subsequent impact of implementation on emerging antibiotic resistance. In most of the trials to date, the average baseline duration of the antibiotic course was longer than is currently standard practice in many UK critical care units. Many other biomarkers are currently being investigated. To be highly useful in clinical practice, it may be necessary to combine these with other novel biomarkers and/or traditional markers of sepsis.

Topics: Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Drug Resistance, Bacterial; Drug Utilization; Humans; Prognosis; Protein Precursors; Sepsis; United Kingdom

Infection and/or sepsis biomarkers should help to make the diagnosis and thus initiate therapy earlier, help to differentiate between infectious and sterile inflammation, allow the use of more-specific antimicrobials, shorten the time of antimicrobial use, and ideally identify distinct phenotypes that may benefit from specific adjunctive sepsis therapies. Procalcitonin (PCT) was proposed as a sepsis and infection marker more than 15 years ago. Meanwhile, PCT has been evaluated in various clinical settings. In this review the present use of PCT on the ICU and in critically ill patients is summarized, included it's role for diagnosis of severe sepsis and septic shock and antibiotic stewardship with PCT.

Topics: Anti-Infective Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Prognosis; Protein Precursors; Sepsis

Sepsis is one of the most cost-intensive conditions of critically ill patients in intensive care medicine. Furthermore, sepsis is known to be the leading cause of morbidity and of mortality in intensive care patients. Early initiation of antibiotic therapy can significantly reduce mortality. The development of resistance of bacterial species against antibiotics is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently no laboratory marker has been available to distinguish bacterial infections from viral or non-infectious inflammatory responses. However, procalcitonin (PCT) appears to be the first among a large array of inflammatory markers that offers this possibility. Regular procalcitonin measurements can significantly shorten the length of antibiotic therapy, show positive influence on antibiotic costs and have no adverse affects on patient outcome.

Topics: Adult; Algorithms; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Critical Care; Critical Illness; Humans; Protein Precursors; Sepsis; Virus Diseases

Critically ill patients frequently suffer from sepsis or localized infections. Diagnosing sepsis can be a challenge since several of its signs overlap with those found with other inflammatory states. Recognition of localized infections can at times be difficult too. While microbiological cultures of blood or other specimens are frequently used to distinguish infection from non-infectious conditions, this diagnostic technique lacks sensitivity and specificity. In addition, there is often a considerable time delay since bacterial cultures may require 24-48 h for analysis, which may be too long for a treatment decision in critically ill patients. Also, the reliability of microbiological cultures decreases in case of prior antimicrobial therapy. Use of biologic markers such as procalcitonin (PCT) or soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have been suggested to improve recognition of patients with true infection and facilitate decisions of whether or not to treat. Unfortunately, neither PCT nor sTREM-1 fulfill all expectations. Data on the diagnostic value, in particular of sTREM-1, are contradicting. The combination of systemic PCT and local and/or systemic sTREM-1 could be useful in distinguishing patients with infection from those with non-infectious illness, though. Results from several randomized intervention studies on PCT-guided antimicrobial therapy in sepsis or lower respiratory tract infections show the superiority of PCT in clinical decision making. At present, randomized intervention studies on the potential antimicrobial stewardship of sTREM-1 are lacking.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Membrane Glycoproteins; Protein Precursors; Receptors, Immunologic; Triggering Receptor Expressed on Myeloid Cells-1

Procalcitonin is widely reported as a useful biochemical marker to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specificity being 71% (95% CI 67-76) and an area under the summary receiver operator characteristic curve of 0.78 (95% CI 0.73-0.83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes' classification. Phase 2 studies had a low pooled diagnostic odds ratio of 7.79 (95% CI 5.86-10.35). Phase 3 studies showed significant heterogeneity because of variability in sample size (meta-regression coefficient -0.592, p=0.017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null effect in larger studies. Procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients. The findings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Diagnosis, Differential; Emergency Medical Services; Humans; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

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

In daily routine diagnosis, there are few parameters available to monitor critically ill patients and to control the course of therapy in severe inflammations. There are also few reliable parameters differentiating acute bacterial infection from other types of inflammation. Most of the presently used indicators of the inflammatory response, like body temperature, white cell count, erythrocyte sedimentation rate or C reactive protein are unspecific parameters with changing reliability. Procalcitonin is a diagnostic parameter of bacterial infections with systemic reaction of the organism. It is an innovative diagnostic parameter with feature different from other presently available indicators of the inflammatory response. The incidence of noninfectious systemic inflammatory response syndrome associated with coronary artery bypass surgery and the potential role of several inflammatory parameters as early markers of pulmonary dysfunction induced by cardiopulmonary bypass were investigated. Procalcitonin seems to be appropriate parameter indicating the early development of severe noninfectious systemic inflammatory response syndrome and for predicting pulmonary dysfunction secondary to cardiopulmonary bypass. Hence, the review of the data of different authors may lead to the conclusion that because of wide spectrum of indications procalcitonin concentration can be used for differential diagnosis of bacterial versus non-bacterial inflammation, as monitoring parameter in critically ill patients, the course of disease, treatment control evaluating the effectiveness of antibacterial treatment, for evaluation of high risk patients to see if there are no postoperative bacterial complications as a prognostic indicator.

Topics: Acute Disease; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Coronary Artery Bypass; Critical Care; Critical Illness; Diagnosis, Differential; Humans; Inflammation; Lung Diseases; Monitoring, Physiologic; Protein Precursors; Risk Factors; Systemic Inflammatory Response Syndrome; Time Factors

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Diagnosis, Differential; Glycoproteins; Humans; Predictive Value of Tests; Protein Precursors; Systemic Inflammatory Response Syndrome

Bacteremia is a leading cause of mortality and morbidity in critically ill adults. No previous randomized controlled trials have directly compared shorter versus longer durations of antimicrobial treatment in these patients.. This is a multicenter pilot randomized controlled trial in critically ill patients with bacteremia. Eligible patients will be adults with a positive blood culture with pathogenic bacteria identified while in the intensive care unit. Eligible, consented patients will be randomized to either 7 days or 14 days of adequate antimicrobial treatment for the causative pathogen(s) detected on blood cultures. The diversity of pathogens and treatment regimens precludes blinding of patient and clinicians, but allocation concealment will be extended to day 7 and outcome adjudicators will be blinded. The primary outcome for the main trial will be 90-day mortality. The primary outcome for the pilot trial is feasibility defined by (i) rate of recruitment exceeding 1 patient per site per month and (ii) adherence to treatment duration protocol  ≥  90%. Secondary outcomes include intensive care unit, hospital and 90-day mortality rates, relapse rates of bacteremia, antibiotic-related side effects and adverse events, rates of Clostridium difficile infection, rates of secondary infection or colonization with antimicrobial resistant organisms, ICU and hospital lengths of stay, mechanical ventilation and vasopressor duration in intensive care unit, and procalcitonin levels on the day of randomization, and day 7, 10 and 14 after the index blood culture.. The BALANCE pilot trial will inform the design and execution of the subsequent BALANCE main trial, which will evaluate shorter versus longer duration treatment for bacteremia in critically ill patients, and thereby provide an evidence basis for treatment duration decisions for these infections.. The Pilot Trial was registered on 26 September 2014.. NCT02261506.

Topics: Anti-Bacterial Agents; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Canada; Clinical Protocols; Critical Illness; Drug Administration Schedule; Feasibility Studies; Humans; Intensive Care Units; Length of Stay; Pilot Projects; Protein Precursors; Research Design; Respiration, Artificial; Time Factors; Treatment Outcome; Vasoconstrictor Agents

Accurate biomarkers of the acute respiratory distress syndrome (ARDS) may help risk stratification and management. We assessed the relation between several biomarkers and the severity, course and outcome of late onset ARDS in 101 consecutive critically ill patients with new onset fever.. On study days 0, 1, 2 and 7 we measured angiopoietin-2 (ANG2), pentraxin-3 (PTX3), interleukin-6 (IL-6), procalcitonin (PCT) and midregional proadrenomedullin (proADM). ARDS was defined by the Berlin definition and by the lung injury score (LIS).. At baseline, 48% had ARDS according to the Berlin definition and 86% according to the LIS. Baseline markers poorly predicted maximum Berlin categories attained within 7 days, whereas ANG2 best predicted maximum LIS. Depending on the ARDS definition, the day-by-day area under the receiver operating characteristic curves suggested greatest monitoring value for IL-6 and PCT, followed by ANG2. ANG2 and proADM predicted outcome, independently of disease severity.. Whereas IL-6 and PCT had some disease monitoring value, ANG2 was the only biomarker capable of both predicting the severity, monitoring the course and predicting the outcome of late onset ARDS in febrile critically ill patients, irrespective of underlying risk factor, thereby yielding the most specific ARDS biomarker among those studied.

Topics: Adrenomedullin; Adult; Aged; Angiopoietin-2; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fever; Humans; Interleukin-6; Lung Injury; Male; Middle Aged; Protein Precursors; Respiratory Distress Syndrome; Serum Amyloid P-Component; Severity of Illness Index

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

A continued need exists for effective diagnostic biomarkers in bacterial sepsis among critically ill patients, despite increasing use of available biomarkers such as procalcitonin (PCT). Interleukin-27 (IL-27) has shown early promise in a recent preliminary study, exhibiting high specificity and positive predictive values for bacterial infection in critically ill children. This validation study was performed to assess the value of IL-27 in predicting bacterial infection among patients admitted to the pediatric intensive care unit and to compare its performance with that of PCT.. A single-center (n = 702) prospective study was performed comparing both IL-27 and PCT levels between bacterially infected and uninfected cohorts in the pediatric intensive care unit. Infected status was determined by a chart review by an intensivist blinded to biomarker results. Formal performance comparisons included calculations of receiver operating characteristic (ROC) curves for IL-27 and PCT individually in addition to a combination strategy using a decision tree generated by classification and regression tree (CART) methodology. Secondary analysis focusing on subjects with documented bloodstream infections was performed.. The overall infection rate was 27 %. ROC curves for the primary analysis yielded areas under the curve (AUCs) of 0.64 (0.59 to 0.68) for IL-27 and 0.61 (0.56 to 0.65) for PCT. Secondary analysis defining infected status exclusively through positive blood cultures yielded AUCs of 0.75 (0.68 to 0.81) for IL-27 and 0.64 (0.57 to 0.71) for PCT, with a specificity of 95 % (92 % to 97 %) for the prior established IL-27 cut-point value of at least 5.0 ng/ml. Similar AUCs were found for the subset of immunocompromised patients. In a CART-derived analysis taking immunocompromised status into consideration, a combination of IL-27 and PCT yielded an AUC of 0.81 (0.75 to 0.86), statistically improved from either IL-27 or PCT alone.. Despite having a modest predictive value for infection independent of source, IL-27 may serve as a useful biomarker in estimating risk of bacterial infection among critically ill pediatric patients with bloodstream infections. In particular, among immunocompromised subjects, this diagnostic biomarker may be helpful either alone or using a combination strategy with other available biomarkers.

Topics: Adolescent; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Interleukins; Male; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

The empiric antibiotic therapy can result in antibiotic overuse, development of bacterial resistance and increasing costs in critically ill patients. The aim of the present study was to evaluate the effect of procalcitonin (PCT) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit (ICU) with systemic inflammatory response syndrome (SIRS). A total of 60 patients were enrolled in this study and randomly divided into two groups, cases that underwent antibiotic treatment based on serum level of PCT as PCT group (n=30) and patients who undergoing antibiotic empiric therapy as control group (n=30). Our primary endpoint was the use of antibiotic treatment. Additional endpoints were changed in clinical status and early mortality. Antibiotics use was lower in PCT group compared to control group (P=0.03). Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ (P=0.88). Patients in PCT group had a significantly shorter median ICU stay, four days versus six days (P=0.01). However, hospital stay was not statistically significant different between two groups, 20 days versus 22 days (P=0.23). Early mortality was similar between two groups. PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay, and we found no differences in clinical outcomes and early mortality rates between the two studied groups.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Organ Dysfunction Scores; Patient Admission; Prospective Studies; Protein Precursors; Sepsis; Single-Blind Method; Systemic Inflammatory Response Syndrome

To Compare the clinical efficacy and safety of meropenem with a 3-hour extended infusion or conventional 30-minute infusion regimen in treatment of hospital acquired pneumonia (HAP) in intensive care unit (ICU) patients.. An open-label randomized controlled clinical trial was conducted. 100 HAP patients, admitted to ICU of Qilu Hospital of Shandong University, who needed meropenem therapy were enrolled from September 1st, 2012 to September 30th, 2013. The patients were randomly divided into two groups. Patients who did not conform to the study protocol were excluded. A total of 78 patients were included for the study of clinical efficacy evaluation, with 38 cases in study group, and 40 in control group. The patients in study group received intravenous 1 g of meropenem (dissolved in 40 mL saline) within 10 minutes, and followed by the remaining 750 mg by continuous intravenous infusion for 3 hours, and the treatment was repeated every 8 hours. The patients in control group received meropenem by injection of 1 g (dissolved in 40 mL saline), i.e. by intravenous infusion within 30 minutes every 8 hours. This regime was carried out for at least 7 days. Clinical efficacy, bacterial clearance rate, improvement of critical illness scoring, and safety were observed and compared after meropenem withdrawal between two groups.. Compared with control group, the clinical cure rate and 28-day survival rate in study group were significantly increased [clinical cure rate: 71.1% (27/38) vs. 42.5% (17/40), χ² = 6.461, P=0.011; survival rate: 81.6% (31/38) vs. 60.0% (24/40), χ² = 4.364, P=0.037]. The improvement of clinical pulmonary infection score (CPIS) and sequential organ failure assessment (SOFA) score in study group were more marked than those in control group (difference of CPIS score: -3.47 ± 2.48 vs. -1.50 ± 2.48, t=-3.513, P=0.001; difference of SOFA score: -2.10 ± 2.38 vs. -1.00 ± 2.21, t=-0.800, P=0.037). There were no significant differences in duration of meropenem treatment, acute physiology and chronic health evaluation II (APACHEII) score, procalcitonin (PCT), duration of mechanical ventilation, ICU stay days, secondary infection, and bacterial clearance rate between two groups. The main adverse reactions observed were transient elevation of liver enzymes and diarrhea in both groups, but no significant difference in their incidence was found between study and control groups [elevated liver enzymes: 28.9% (11/38) vs. 30.0% (12/40), χ² = 0.010, P=0.919; diarrhea: 7.9% (3/38) vs. 10.0% (4/40), χ² = 0.000, P=1.000].. Compared with conventional regime of 30-minute infusion of meropenem in the treatment of HAP in ICU patients, the clinical efficacy can be improved, the severity of the disease can be reduced, the recovery of organ failure and long-term prognosis can be improved with 3 hour extended infusion of meropenem.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Infusions, Intravenous; Intensive Care Units; Meropenem; Pneumonia; Protein Precursors; Respiration, Artificial; Thienamycins; Time Factors

The role of procalcitonin (PCT), a widely used sepsis biomarker, in critically ill patients with sepsis is undetermined.. To investigate the effect of a low PCT cut-off on antibiotic prescription and to describe the relationships between PCT plasma concentration and sepsis severity and mortality.. This was a multicenter (11 Australian intensive care units [ICUs]), prospective, single-blind, randomized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours. The primary outcome was the cumulative number of antibiotics treatment days at Day 28.. PCT was measured daily while in the ICU. A PCT algorithm, including 0.1 ng/ml cut-off, determined antibiotic cessation. Published guidelines and antimicrobial stewardship were used in all patients. Primary analysis included 196 (PCT) versus 198 standard care patients. Ninety-three patients in each group had septic shock. The overall median (interquartile range) number of antibiotic treatment days were 9 (6-21) versus 11 (6-22), P = 0.58; in patients with positive pulmonary culture, 11 (7-27) versus 15 (8-27), P = 0.33; and in patients with septic shock, 9 (6-22) versus 11 (6-24), P = 0.64; with an overall 90-day all-cause mortality of 35 (18%) versus 31 (16%), P = 0.54 in the PCT versus standard care, respectively. Using logistic regression, adjusted for age, ventilation status, and positive culture, the decline rate in log(PCT) over the first 72 hours independently predicted hospital and 90-day mortality (odds ratio [95% confidence interval], 2.76 [1.10-6.96], P = 0.03; 3.20 [1.30-7.89], P = 0.01, respectively).. In critically ill adults with undifferentiated infections, a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25% reduction in duration of antibiotic treatment. Clinical trial registered with http://www.anzctr.org.au (ACTRN12610000809033).

Topics: Adult; Aged; Algorithms; Anti-Bacterial Agents; Australia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Single-Blind Method

: 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

To assess the value of procalcitonin (PCT) measurement to differentiate infection from non-infection in critically ill patients requiring long-term immunosuppressive therapy.. A prospective study was conducted in patients with underlying diseases requiring corticosteroids or chemotherapy in ICU from January 2008 to December 2009. Patients were divided into the infection group and the non-infection group and their PCT levels were compared.. A total of 103 patients (65 women) were enrolled in this prospective study [aged (47.9 ± 21.9) years old] with 84 in the infection group and 19 in the non-infection group. The baseline level of PCT was significantly higher in infection than in non-infection patients [2.58 (0.08 - 44.65) pg/L vs 0.62 (0.15 - 6.00) pg/L, P = 0.002]. Different levels of PCT were manifested in different pathogen groups with 3.41 (0.45 - 44.65) pg/L in bacteria infection, 0.99 (0.28 - 6.67) pg/L in fungus infection, 0.11 (0.08 - 0.20) pg/L in virus infection group (P = 0.018). The AUC(ROC) of PCT was 0.867 for diagnostic bacterial infection. By multivariate analysis, the factors associated with the level of PCT were bacteria infection (OR 5.1, P = 0.031) and septic shock (OR 7.5, P = 0.027), while the factors not associated with the level of PCT were age, renal function, infection site and prognosis (P > 0.05).. The level of PCT is increased in the critically ill patients requiring immunosuppressive therapy with infection and it can be used for diagnosis for bacterial infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Young Adult

Systemic inflammatory response syndrome (SIRS) and sepsis remain the leading cause of death in the critically ill. A reduction in the antioxidant capacity, including selenoenzymes that are dependent on selenium (Se), could be a contributing factor. Se supplementation in septic patients have yielded conflicting results. We hypothesized that a high-dose Se supplementation would (1) improve markers of inflammation, nutrition and antioxidant defence, and (2) decrease mortality.. This prospective, randomized, open-label, single-centre clinical trial included 150 patients with SIRS/sepsis and a SOFA score of >5. Patients in the Se+ group (n = 75) received Se for 14 days (1,000 μg on day 1,500 μg/day on days 2-14). Patients in both the control (Se-) group (n = 75) and the Se+ group received a standard Se dose (<75 μg/day). Plasma Se, whole-blood glutathione peroxidase (GPx) activity, C-reactive protein (CRP), procalcitonin (PCT), albumin, prealbumin and cholesterol levels, along with APACHE II and SOFA scores, were determined at baseline and on days 1-7 and day 14. Mortality was assessed at day 28.. Plasma Se and GPx activity were increased in the Se+ group from day 1 onwards. Negative correlations were demonstrated between plasma Se, CRP (P = 0.035), PCT (P = 0.022) and SOFA (P = 0.001) at admission but not on days 7 or 14. Prealbumin and cholesterol increased in the Se+ group versus the respective baselines. Mortality was similar between groups, with no gender differences.. High-dose Se substitution in patients with SIRS/sepsis increased plasma Se and GPx levels, but did not reduce mortality. Markers of inflammation were reduced similarly in both groups.

Topics: Adult; Aged; Antioxidants; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Multiple Organ Failure; Prealbumin; Prospective Studies; Protein Precursors; Selenium; Sepsis

Non-intensive care unit (ICU) cohorts have shown an association between inflammatory disturbances and delirium, though these relationships have not been studied in critically ill patients. This study sought to investigate the relationship between two inflammatory biomarkers, procalcitonin and C-reactive protein (CRP), and duration of acute brain dysfunction in ventilated patients.. Patients enrolled in the Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial were assessed daily for delirium using the Confusion Assessment Method-ICU. Plasma levels of procalcitonin and CRP were obtained within 24 hours of enrollment. Proportional odds logistic regression was used to examine the association between procalcitonin and CRP separately with delirium/coma-free days, adjusting for age, acute physiology score (APS) of the Acute Physiology And Chronic Health Evaluation (APACHE) II, sedation group (dexmedetomidine vs. lorazepam), and sepsis. Secondary analyses examined the association of these markers with other organ dysfunctions and 28-day survival.. Eighty-seven patients were included in this analysis. The median age of the patients was 60 years with APACHE II scores of 28; 68% had sepsis within 48 hours of admission. Higher levels of procalcitonin were associated with fewer delirium/coma-free days [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3 to 1.0; P = 0.04], whereas higher CRP levels showed trends towards fewer delirium/coma-free days (OR, 0.6; 95% CI, 0.3 to 1.1; P = 0.08). Similar relationships were found regardless of the presence of sepsis. No associations were found between procalcitonin or CRP with 28-day survival (P = 0.40 and 0.16, respectively).. In our pilot study, high baseline inflammatory biomarkers predicted prolonged periods of acute brain dysfunction, implicating inflammation as an important mechanism in the pathophysiology of delirium and coma during critical illness, irrespective of whether patients had sepsis or not.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Delirium; Female; Humans; Male; Middle Aged; Patient Admission; Pilot Projects; Predictive Value of Tests; Prospective Studies; Protein Precursors; Respiration, Artificial; Time Factors

Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting.. In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667.. Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001).. A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes.. Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.

Topics: Adult; Aged; Algorithms; Anti-Bacterial Agents; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Decision Support Techniques; Drug Administration Schedule; Drug Monitoring; Drug Resistance, Bacterial; Female; France; Humans; Intensive Care Units; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Practice Guidelines as Topic; Prospective Studies; Protein Precursors; Time Factors; Treatment Outcome

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

Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients.. Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients.. For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).

Topics: Adolescent; Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Male; Protein Precursors; Sepsis

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

Studies of the diagnostic accuracy of most laboratory tests for early-onset neonatal sepsis have yielded variable results. We investigated whether some of this variation might be attributable to differences in population baseline severity and risk status as well as to specific ante- and perinatal variables, independent of the presence of neonatal infection.. The Score for Neonatal Acute Physiology (SNAP) was used to define illness severity, with SNAP Perinatal Extension (SNAP-PE) used to define the combined physiologic and perinatal mortality risk. A total of 134 ill newborns (19 with early-onset infection and 115 with no infection) were available for simultaneous analysis of the association of SNAP, SNAP-PE, and maternal and perinatal variables with C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) concentrations at birth and at 24 and 48 h of life.. Early-onset neonatal infection was associated with significant increases in CRP, IL-6, and PCT concentrations at all three time points, independent of illness severity. However, among babies without infection, higher SNAP and SNAP-PE scores were associated with higher IL-6 concentrations at birth. Certain maternal or perinatal variables altered IL-6 and PCT values in the infected as well as in the uninfected neonates. However, if different cutoff points were used at any of the three neonatal ages, PCT sensitivity and specificity were greater than those of CRP or IL-6.. Illness severity and risk status are unlikely to interfere with the use of CRP and PCT for detection of early-onset neonatal sepsis. In contrast, the diagnostic value of IL-6 at birth may be altered by physiologic severity and risk indexes. The reliability of CRP, IL-6, and PCT for the diagnosis of early-onset neonatal infection requires specific cutoff values for each evaluation time point over the first 48 h of life.

Topics: Adult; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Data Interpretation, Statistical; Female; Humans; Infant, Newborn; Inflammation; Interleukin-6; Pregnancy; Pregnancy Complications; Protein Precursors; Risk Factors; Severity of Illness Index; Time Factors

: In critically ill patients, severe infection and systemic inflammation due to non-infectious causes produce very similar clinical presentations, and traditional infection markers do not always differentiate these two conditions. Both procalcitonin and neopterin have been suggested to aid in the early diagnosis of bacterial infections and in differentiating bacterial infections from systemic inflammatory, non-infectious diseases or from viral infections.. : Procalcitonin (PCT) and neopterin were analyzed in 208 ICU patients who developed acute fever or septic shock. Blood samples were taken every 8th h within 48 h of the onset of fever or septic shock.. : A total 162/208 of patients had infection, the most common location being the respiratory tract. Mortality was higher in infected patients (31.4% vs. 10.9%; P < 0.01). The optimum cut-off levels in identifying patients with infection of daily peak PCT were 0.8 microg/L on day 1 and 0.9 microg/L on day 2, and both sensitivity (67.7% and 60.9%, respectively) and specificity (47.8% and 63%) were poor. Accordingly, the optimum cut-off values of peak neopterin were 18 and 16 pg/L. The sensitivity was 62.7% on day 1 and 69.3% on day 2, while specificity was correspondingly 78.3% and 67.9%. There were no significant differences between the markers in discriminating between patients with infection or inflammation. Both PCT and neopterin increased with the severity of infection. They were higher in non-survivors.. : PCT and neopterin were equally effective, although not very accurate in differentiating between infection and inflammation in critically ill patients. Neopterin was more specific than PCT, suggesting that neopterin is related to the activity of inflammatory response.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fever; Hospital Mortality; Humans; Infections; Male; Middle Aged; Neopterin; Protein Precursors; Sepsis; Shock; Survivors

Rapid and accurate prediction for sepsis remains a challenge in surgical intensive care units. Detection of individual biomarkers is often of marginal usefulness, and several biomarkers are difficult to measure in the clinical setting. The aim of this study was to evaluate the diagnostic and prognostic performance of three routine biomarkers, procalcitonin (PCT), B-type natriuretic peptide (BNP), and lymphocyte percentage, as individual or in combination for sepsis in surgical critically ill patients.. Circulating PCT, BNP, and lymphocyte percentage were measured in surgical patients on admission to the intensive care unit. A bioscore system combining these biomarkers was constructed. All studied variables were analyzed according to the diagnosis and clinical outcomes of sepsis.. A total of 320 consecutive patients were included in the analysis. One hundred fifty-six patients presented with sepsis. In the patients with sepsis, levels of PCT and BNP increased and lymphocyte percentage decreased. For individual biomarkers, PCT achieved the best area under the curve for the diagnosis of sepsis, whereas the diagnostic performance of the bioscore was better than that of each individual biomarker (area under the curve, 0.914 [95% confidence interval, 0.862-0.951]). Levels of BNP and bioscore increased in nonsurvivors in the entire cohort, but the accuracy of these two variables for mortality prediction was lower than that shown by Acute Physiology and Chronic Health Evaluation II score. Furthermore, bioscore failed to predict outcomes in septic patients.. A simple bioscore combining PCT together with BNP and lymphocyte percentage improves the diagnostic accuracy for sepsis in surgical critically ill patients but fails to predict outcomes in surgical patients with sepsis.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Decision Support Techniques; Female; Humans; Lymphocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Prognosis; Prospective Studies; Protein Precursors; Sepsis

The objective of this study was to assess the diagnostic accuracy of C-reactive protein (CRP), procalcitonin (PCT), and cellular immune markers levels in sepsis. This was a prospective observational study in adult intensive care unit (ICU) patients, between 2012 and 2014. The 8-color flow cytometric biomarker panel included CD64, CD163, and HLA-DR. Index test results were compared with sepsis, using receiver operating characteristic curve analyses. Multivariate logistic regression assessed the relationship of sets of markers with the probability of sepsis. Of 219 enrolled patients, 120 had sepsis. C-statistic was the highest for CRP (0.86) followed by neutrophil CD64 expression (0.83), procalcitonin (0.82), and Acute Physiology and Chronic Health Evaluation (APACHE) IV (0.72). After adjustment for APACHE IV, the combination of CRP, PCT, and neutrophil CD64 measure remained a significant predictor of sepsis with an excellent AUC (0.90). In a targeted ICU population at increased risk of sepsis, CRP, PCT, and neutrophil CD64 combined improve the diagnostic accuracy of sepsis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Chemical Analysis; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Double-Blind Method; Female; Flow Cytometry; Humans; Leukocytes; Male; Membrane Proteins; Middle Aged; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

An accurate and readily available biomarker for identifying patients with complicated intra-abdominal infection needing special attention in critical care units because of their greater risk of dying would be of value for intensivists.. A multi-center, observational, retrospective study explored blood lactate, C-reactive protein (CRP), and procalcitonin (PCT) concentrations, and also Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS II) as mortality predictors in all adult patients with complicated intra-abdominal infection (cIAI) admitted to Surgical Critical Care Units (SCCUs) for ≥48 h in four Spanish hospitals (June 2012-June 2013). Logistic regression models (step-wise procedure) were constructed using as dependent variables "intra-SCCU mortality" or "overall mortality," and variables showing differences (p≤0.1) in bivariate analyses as independent variables.. One hundred twenty-one cases were included. Mortality intra-SCCU (R(2)=0.189, p=0.001) was associated with SAPS II (categorized as high if ≥47) (OR=9.55; 95% CI, 1.09-83.85; p=0.042) and 24 h-lactate (≥5.87 categorized as high) (OR=6.90; 95% CI, 1.28-37.08). Overall mortality (R(2)=0.275, p=0.001) was associated with peak PCT (≥100 categorized as high) (OR=11.28; 95% CI, 1.80-70.20), peak lactate (≥1.8 categorized as high) (OR=8.86; 95% CI, 1.51-52.10) and SOFA at admission (≥7 categorized as high) (OR=8.14; 95% CI, 1.69-39.20), but was predicted better (R(2)=0.275, p=0.001) by a single dummy variable (high peak PCT-high peak lactate concentrations) (OR=99.11; 95% CI, 5.21-1885.97; p=0.002).. In the present study, SAPS II and 24 h-lactate concentrations predicted intra-SCCU mortality whereas overall mortality was predicted better by concurrent high PCT and lactate peak concentrations than by clinical scores or by each biomarker separately.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intraabdominal Infections; Lactic Acid; Male; Middle Aged; Prognosis; Protein Precursors; Retrospective Studies; Severity of Illness Index; Spain; Survival Analysis; Young Adult

To evaluate interleukin-27 (IL-27) as a sepsis diagnostic biomarker in critically ill adults with sepsis.. A retrospetive study was conducted. A total of 176 systemic inflammatory response syndrome (SIRS) patients in Department of Critical Care Medicine of Xinxiang Medical College First Affiliated Hospital from March to November in 2014 were enrolled. The patients were divided into no sepsis group (n=66), pulmonary originated sepsis group (n=65), and non-pulmonary originated sepsis group (n=45). Plasma IL-27 and procalcitonin (PCT) were determined with enzyme linked immunosorbent assay (ELISA). Receiver operating characteristic curve (ROC) and classification and regression tree methodology was used to evaluate diagnostic biomarker performance.. The proportion of patients in pulmonary original sepsis group whose body temperature in line with SIRS criteria was significantly higher than no sepsis group (66.2% vs. 44.5%, P<0.05), and they were easy to suffer from tumor (44.6% vs. 22.7%, P<0.05). The proportion of patients in non-pulmonary originated sepsis group whose white blood cell count in line with SIRS criteria was significantly higher than no sepsis group (68.9% vs. 42.7%, P<0.05). It indicated that patients in pulmonary originated sepsis group and non-pulmonary originated sepsis group were more in line with SIRS criteria compared with no sepsis group. It was shown by ROC curve that IL-27 and PCT was not effective in discriminating sepsis among unselected patients showing symptoms and signs of SIRS. The area under the curve (AUC) was 0.59 [95% confidence interval (95%CI)=0.49-0.65] and 0.61 (95%CI=0.55-0.71). According to the further analysis from different infection sources, the highest AUC was 0.71 (95%CI=0.59-0.79) for IL-27 in patients with a non-pulmonary originated sepsis. A decision tree incorporating IL-27, PCT, and age had an AUC of 0.78 (95%CI=0.71-0.87) in patients with a non-pulmonary originated sepsis, which was higher than IL-27 [0.71(95%CI=0.59-0.79)] or PCT [0.65 (95%CI=0.57-0.78)]. Compared to that of pediatric cohort with sepsis, lower expression of IL-27 was found in adult patients.. IL-27 performed overall poorly as a sepsis diagnostic biomarker in adults. IL-27 may be a more reliable diagnostic biomarker for sepsis in children than in adults. The combination of IL-27 and PCT can reasonably estimate the risk of sepsis in subjects with a non-pulmonary originated sepsis.

Topics: Adult; Area Under Curve; Biomarkers; Blood Pressure; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Humans; Interleukins; Leukocyte Count; Protein Precursors; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

To evaluate the diagnostic and prognostic value of the serum procalcitonin (PCT) level in the non-acquired immune deficiency syndrome (AIDS) immunocompromised critically ill patients suspected to have infection.. A retrospective study was conducted in the non-AIDS immunocompromised patients who were admitted to Department of Critical Care Medicine of Xiangya Hospital, Central South University during January 2011 to December 2014. Demographic characteristics, underlying disease, acute physiology and chronic health evaluation II (APACHEII) score at admission, and clinical records including baseline and peak levels of temperature, white blood count (WBC), PCT, and survival rate within 28 days, infection focus, infectious agents (bacterial, fungi or mixed infection), and the severity of infection (sepsis, severe sepsis, or septic shock) were recorded. Receiver operating characteristic (ROC) curve was plotted, and the diagnostic and protective value of above parameters was evaluated.. A total of 98 patients (43 male and 55 female) were enrolled in the study with a median age of 44 (28, 52) years old and a median APACHEII score of 17 (11, 20); 47 with malignant hematological tumor, 45 with autoimmune diseases, and 6 post solid organ transplantation. Among them 53 patients (54.1%) died within 28 days. Twenty-seven patients were diagnosed as systemic inflammatory response syndrome (SIRS) without infection. Among 71 patients with infection, 45 were diagnosed as bacterial infection, 10 with fungal infection, and 16 with mixed infection. Sepsis was diagnosed in 7 patients, severe sepsis in 32 patients, and septic shock in 32 patients. (1) There was no statistical significance in the baseline and peak levels of PCT and WBC, or baseline level of temperature between the groups of SIRS patients without infection and infected patients. The peak level of temperature was significantly higher in the patients with infection as compared with that of the SIRS without infection patients [centigrade: 39.4 (38.9, 40.0) vs. 38.8 (37.8, 39.2), Z=-3.268, P=0.001]. It was showed by subgroup analysis that in patients with hematological malignant disease or autoimmune diseases, higher level of body temperature was found in infection group compared with non-infection SIRS group [centigrade: 39.5 (39.0, 40.0) vs. 39.0 (38.4, 39.4), Z=-2.349, P=0.019; 39.0 (38.4, 39.5) vs. 38.2 (37.0, 38.9), Z=-2.221, P=0.026]. (2) The baseline level of PCT (μg/L) were 0.54 (0.20, 4.19), 2.78 (0.50, 9.54), 1.00 (0.45, 6.89), and 0.22 (0.07, 1.86) in non-infection SIRS patients or the patients with bacterial, fungal, and mixed infection, respectively. The peak level of PCT (μg/L) were 4.19 (1.95, 13.42), 12.37 (3.82, 45.89), 1.82 (0.49, 17.86), and 5.14 (2.66, 12.62), respectively, in each subgroup. When the comparison was conducted among the patients with different infectious agent, the baseline level of PCT in patients with bacterial infection was significantly higher than that in SIRS patients without infection (P=0.026) and mixed infection patients (P=0.001), and the peak level of PCT was significantly higher than that in the SIRS patients without infection (P=0.009) and the patients with fungal infection (P=0.016). ROC curve showed that the higher value was found in the baseline and peak levels of PCT for diagnosis of septic shock in all patients [ area under ROC curve (AUC) of baseline level=0.681±0.054, P=0.001; AUC of peak level=0.690±0.054, P=0.002], and the same value was. The serum level of PCT is found to be a reliable marker for the diagnosis of bacterial infection in immunocompromised critical patients, especially in those with hematologic malignancy. Additionally, PCT provides a useful tool for evaluating the severity of infection and the prognosis of critically ill patients.

Topics: Adult; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Middle Aged; Prognosis; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Survival Rate; Systemic Inflammatory Response Syndrome

The purpose of this study was to confirm the prognostic value of pancreatic stone protein (PSP) in patients with severe infections requiring ICU management and to develop and validate a model to enhance mortality prediction by combining severity scores with biomarkers.. We enrolled prospectively patients with severe sepsis or septic shock in mixed tertiary ICUs in Switzerland (derivation cohort) and Brazil (validation cohort). Severity scores (APACHE [Acute Physiology and Chronic Health Evaluation] II or Simplified Acute Physiology Score [SAPS] II) were combined with biomarkers obtained at the time of diagnosis of sepsis, including C-reactive-protein, procalcitonin (PCT), and PSP. Logistic regression models with the lowest prediction errors were selected to predict in-hospital mortality.. Mortality rates of patients with septic shock enrolled in the derivation cohort (103 out of 158) and the validation cohort (53 out of 91) were 37% and 57%, respectively. APACHE II and PSP were significantly higher in dying patients. In the derivation cohort, the models combining either APACHE II, PCT, and PSP (area under the receiver operating characteristic curve [AUC], 0.721; 95% CI, 0.632-0.812) or SAPS II, PCT, and PSP (AUC, 0.710; 95% CI, 0.617-0.802) performed better than each individual biomarker (AUC PCT, 0.534; 95% CI, 0.433-0.636; AUC PSP, 0.665; 95% CI, 0.572-0.758) or severity score (AUC APACHE II, 0.638; 95% CI, 0.543-0.733; AUC SAPS II, 0.598; 95% CI, 0.499-0.698). These models were externally confirmed in the independent validation cohort.. We confirmed the prognostic value of PSP in patients with severe sepsis and septic shock requiring ICU management. A model combining severity scores with PCT and PSP improves mortality prediction in these patients.

Topics: Biomarkers; Brazil; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Hospital Mortality; Humans; Lithostathine; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index; Switzerland

The diagnostic value of procalcitonin (PCT) for patients with autoimmune diseases (AID) remains controversial and few studies focused on ICU patients. We sought to determine its diagnostic and prognostic values in this clowd.. A prospective observational study was conducted in AID patients admitted to the ICU. Serum PCT levels were measured on ICU admission and subsequently at days 1, 3, 5 and 7, and peak PCT levels within 24 h (PCTpeak) were analyzed the utility for bacterial infection. The relationship of PCTpeak and SOFA score and severity of sepsis was performed correlation analysis. The change of PCT over time reflected as PCT clearance was compared to ICU 28-day mortality.. One hundred twelve patients were divided into bacterial infection group (group I, n = 54) and nonbacterial condition group (group II, n = 58). The median PCTpeak (range, μg/L) was higher in the group I than that in the group II (1.95 [0.38-37.56] vs. 0.64 [0.05-7.83], p = 0.002). PCTpeak had the best single predictor of bacterial infection (area under the curve [AUC], 0.902, p < 0.001) with a sensitivity of 79.6 % and a specificity of 89.6 % at the threshold of 0.94 μg/L. PCTpeak was also positive correlation with severity of sepsis (r = 0.731, p = 0.002), but its correlation with SOFA score was only found in subjects with bacterial infection (r = 0.798, p < 0.001). Importantly, the 5-day PCT clearance (PCTc-d5), rather than absolute PCT values, could earlier discriminate survivors (n = 73) from nonsurvivors (n = 39) (68.8 ± 9.8 vs. 21.8 ± 17.5 %, p < 0.001, respectively). PCTc-d5 < 50 % was an independent predictor of mortality (odds ratio 5.1, 95 % confidence interval 3.5 to 7.5; p = 0.001).. In critically ill patients with AID, elevated PCT levels are valuable for bacterial infection and are significantly positive correlation with the septic severity. Five-day PCT clearance may provide independent prognostic information. Larger, prospective trials are warranted to confirm the benefit.

Topics: Adult; Aged; Autoimmune Diseases; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Treatment Outcome

Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting.. A prospective international multicenter cohort study.. Seven different emergency departments in Sweden, Canada, and the United States.. Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count).. None.. Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (>30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve=0.80). The performance of heparin-binding protein was confirmed in the validation cohort.. In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.

Topics: Adult; Aged; Antimicrobial Cationic Peptides; Area Under Curve; Biomarkers; Blood Proteins; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Canada; Carrier Proteins; Cause of Death; Cohort Studies; Critical Illness; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Internationality; Male; Middle Aged; Multiple Organ Failure; Predictive Value of Tests; Prospective Studies; Protein Precursors; Risk Assessment; Sepsis; Survival Analysis; Sweden; Systemic Inflammatory Response Syndrome; Treatment Outcome; United States

The prognostic role of serum procalcitonin level in critically ill patients with ventilator-associated pneumonia was unclear. The aim of our study was to investigate the relationship between serum procalcitonin level and mortality risk in critically ill patients with ventilator-associated pneumonia.. Data of critically ill patients with ventilator-associated pneumonia were retrospectively collected. Demographics, comorbidities, and serum procalcitonin level were extracted from electronic medical records. The primary outcome was mortality within two months after diagnosis. Multivariable Cox regression analyses were performed to assess the prognostic role of serum procalcitonin level in those patients.. A total of 115 critically ill patients with ventilator-associated pneumonia were enrolled in our study. Serum procalcitonin level was not associated with age, gender, or other comorbidities. Univariate Cox regression model showed that high serum procalcitonin level was associated increased risk of morality within 2 months after diagnosis (OR = 2.32, 95% CI 1.25-4.31, P = 0.008). Multivariable Cox regression model showed that high serum procalcitonin level was independently associated increased risk of morality within 2 months after diagnosis (OR = 2.38, 95% CI 1.26-4.50, P = 0.008).. High serum procalcitonin level is an independent prognostic biomarker of mortality risk in critically ill patients with ventilator-associated pneumonia, and it's a promising biomarker of prognosis in critically ill patients.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Critical Illness; Demography; Female; Humans; Intensive Care Units; Male; Odds Ratio; Pneumonia, Ventilator-Associated; Prognosis; Proportional Hazards Models; Protein Precursors; Retrospective Studies; Risk

Acute multiple-trauma induces activation of neuroendocrine system. Nonthyroidal illness syndrome (NTIS) is considered to be associated with adverse outcome in intensive care unit (ICU) patients. This study was aimed to assess dynamic changes of neuroendocrine hormones in patients with polytrauma and their association with the polytrauma score (PTS).. Blood samples from 24 critically ill patients with polytrauma were obtained on 1st, 2nd, 3rd and 7th day after admission to ICU for analysis of thyroid-stimulating hormone (TSH), total triiodothyronine (T3); free triiodothyronine (fT3), total thyroxine (T4), free thyroxine (fT4), growth hormone (GH), prolactin (PRL) and procalcitonin levels.. Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16±5 points on average at the admission to ICU. All patients had normal baseline TSH, T4, fT4, but low T3, and fT3 levels were found in 20% and 33% ICU patients, respectively. On the 7th day after admission to ICU TSH had tendency to increase (p=0.07) and fT4 significantly decreased (p=0.03). The PRL level significantly increased on the 3rd day after admission as compared to 1st day (p=0.04). PTS positively correlated with fT3 (r=0.582, p=0.004) and negatively with fT4 (r=-0.422, p=0.04) at the 1st day in ICU.. Critical illness in patients with polytrauma leaded to trauma severity-dependent alterations of the thyroid axis response early after injury. Our findings suggest that detection of dynamic hormonal response is more appropriate than single measurement. However supplemental therapy for NTIS should be used after more detailed studies are completed.

Topics: Adult; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Critical Illness; Euthyroid Sick Syndromes; Female; Human Growth Hormone; Humans; Intensive Care Units; Male; Middle Aged; Multiple Trauma; Prolactin; Prospective Studies; Protein Precursors; Thyrotropin; Thyroxine; Triiodothyronine

Procalcitonin (PCT) is a relatively new, promising indirect parameter for infection. In the intensive care unit (ICU) it can be used as a marker for sepsis. However, in the ICU there is a need for reliable markers for clinical deterioration in the critically ill patients. This study determines the clinical value of PCT concentrations in recognizing surgical complications in a heterogeneous group of general surgical patients in the ICU.. We prospectively collected PCT concentration data from April 2010 to June 2012 for all general surgical patients admitted to the ICU. Both the relationships between PCT levels and events (diagnostic and therapeutic interventions) as well as between PCT levels and surgical complications (abscesses, bleeding, perforation, ischemia, and ileus) were studied.. PCT concentrations were lower in patients who developed complications than those who did not develop complications on the same day, although not significant (P = 0.27). A 10% increase in PCT levels resulted in a 2% higher complication odds, but again this was not significant (odds ratio [OR], 1.020; 95% confidence interval [CI], 0.961-1.083; P = 0.51). Even a 20% or 30% increase in PCT concentrations did not result in higher complication probability (OR, 1.039; 95% CI, 0.927-1.165 and OR, 1.057; 95% CI, 0.897-1.246). Furthermore, an increase in PCT levels did not show an increase or a reduction in the number of diagnostic and therapeutic interventions.. An increase in PCT levels does not help to predict surgical complications in critically ill surgical patients.

Topics: Abscess; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Hospital Mortality; Humans; Ileus; Intensive Care Units; Ischemia; Male; Middle Aged; Postoperative Hemorrhage; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Surgical Wound Infection

The aim of this study was to investigate the prevalence of endotoxemia in critically ill Japanese patients using the endotoxin activity assay, a newly developed rapid assay of endotoxin. The endotoxin levels (EA levels) in the blood of 314 patients admitted to our university hospital's intensive care unit (ICU) were measured within 24 h of admission, and its correlation with disease severity and outcome examined. In addition, the EA levels in 61 samples from healthy volunteers were measured. EA level was 0.39 ± 0.25 (mean ± SD) in patients admitted to the ICU and 0.10 ± 0.09 in healthy controls. There was less overlap of EA level distribution between patients and controls compared with previous reports measuring EA level in mainly Caucasian populations. Our patients' EA levels were significantly correlated with disease severity criteria and 28-d mortality. When EA and procalcitonin levels were used concomitantly, disease severity could be assessed more precisely than when either marker was used alone. These results suggest that EA level is a useful marker for disease severity assessment and outcome prediction in critically ill patients.

Topics: Adult; Aged; APACHE; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Endotoxemia; Endotoxins; Female; Humans; Male; Middle Aged; Mycoses; Protein Precursors; Retrospective Studies; Systemic Inflammatory Response Syndrome

Utilizing procalcitonin (PCT) levels to limit antimicrobial overuse would be beneficial from a humanistic and economic perspective.. To assess whether introducing PCT at a teaching hospital reduced antimicrobial exposure in critically ill patients.. Patients wereadmitted to the intensive care unit (ICU) for >72 hours with sepsis and/or pneumonia. PCT levels were drawn on admission to the ICU or with new suspected infection, with at least 1 PCT level being drawn at least 48 hours later. Patients were matched in a 1:1 fashion to historical patients on age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, gender, and primary diagnosis. The primary outcome was duration of initial antimicrobial exposure defined as days from initiation of antimicrobial therapy to the intentional discontinuation of therapy by the physician. Secondary end points included length of stay, readmission to the hospital, and relapse of infection.. There were 50 patients in the PCT group and 50 patients in the historical group. The initial duration of antimicrobials was 10 (±4.9) days compared with 13.3 (±7.2), which was statistically significant (P = .0238). The duration of stay in the hospital (13.5 compared with 17.8 days; P = .0299), readmission to the hospital (9 compared with 17; P = .055), and relapse of infection (3 compared with 11; P = .02) were seen less in the PCT group compared with controls.. Introducing PCT levels resulted in a shorter duration of initial antimicrobial therapy and was not associated with adverse treatment outcomes.

Topics: Aged; Anti-Infective Agents; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Critical Illness; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Patient Readmission; Pneumonia; Protein Precursors; Recurrence; Sepsis

To investigate the correlation between serum procalcitonin (PCT) level and pediatric critical illness score (PCIS) and their prognostic values in children with sepsis.. Sixty-one children with sepsis in the pediatric intensive care unit were enrolled. According to PCIS, these patients were divided into non-critical (n=18), critical (n=20), and extremely critical groups (n=23). Within 24 hours after admission, serum levels of PCT, C-reactive protein (CRP), and lactic acid (LA) and routine blood counts were measured. These parameters were compared between the three groups. The Pearson correlation analysis was performed to determine the correlation of PCT with PCIS and other serological parameters. Based on clinical outcomes, these patients were divided into survival (n=39) and death groups (n=22). The PCT, PCIS, and other serological parameters were compared between the two groups.. The serum levels of PCT and CRP in the non-critical group were significantly lower than those in critical group and extremely critical groups (P<0.05), and the two parameters were significantly lower in the critical group than in the extremely critical groups (P<0.05). The extremely critical group had a significantly higher mortality than the critical group non-critical groups (61% vs 35% and 6%, P<0.05). Serum PCT level had a significantly negative correlation with PCIS (r=-0.63, P<0.001) but a significantly positive correlation with serum CRP level (r=0.73, P=0.003). Compared with the death group, the survival group had significantly higher serum levels of PCT and LA (P<0.05) but a significantly lower PCIS (P<0.05).. There is a good correlation between serum PCT level and PCIS. For children with sepsis, the lower the PCIS, the higher the serum PCT level, resulting in a poorer prognosis. A combination of serum PCT and PCIS can be used as an early prognostic indicator in children with sepsis.

Topics: Adolescent; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Male; Prognosis; Protein Precursors; Sepsis

We investigated the diagnostic and prognostic utilities of procalcitonin (PCT), B-type natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in critically ill patients with suspected sepsis, for whom sepsis was diagnosed clinically or based on PCT concentrations.. PCT, BNP, and NGAL concentrations were measured in 340 patients and were followed up in 109 patients. All studied biomarkers were analyzed according to the diagnosis, severity, and clinical outcomes of sepsis.. Clinical sepsis and PCT-based sepsis showed poor agreement (kappa = 0.2475). BNP and NGAL showed significant differences between the two groups of PCT-based sepsis (P = 0.0001 and P < 0.0001), although there was no difference between the two groups of clinical sepsis. BNP and NGAL were significantly different according to the PCT staging and sepsis-related organ failure assessment subscores (P < 0.0001, all). BNP and PCT concentrations were significantly higher in the non-survivors than in the survivors (P = 0.0002) and showed an equal ability to predict in-hospital mortality (P = 0.0001). In the survivors, the follow-up NGAL and PCT concentrations were significantly lower than the initial values (148.7 ng/mL vs. 214.5 ng/mL, P < 0.0001; 0.61 ng/mL vs. 5.56 ng/mL, P = 0.0012).. PCT-based sepsis diagnosis seems to be more reliable and discriminating than clinical sepsis diagnosis. Multimarker approach using PCT, BNP, and NGAL would be useful for the diagnosis, staging, and prognosis prediction in the critically ill patients with suspected sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Infant, Newborn; Lipocalins; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Protein Precursors; Sepsis

The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated. This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit.. BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure. The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis.. Bacterial pneumonia (n=24) and viral pneumonia (n=23) were frequently associated with neutrophilic pleocytosis in BAL fluid. BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P=0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group. In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750-0.960). BAL fluid total WBC count ≥ 510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21. When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07. BAL fluid total WBC count ≥ 510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis.. Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients.

Topics: Adult; Area Under Curve; Bronchoalveolar Lavage Fluid; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Diagnosis, Differential; Humans; Leukocyte Count; Likelihood Functions; Odds Ratio; Pneumonia, Bacterial; Pneumonia, Viral; Protein Precursors; ROC Curve; Sensitivity and Specificity

We recently identified interleukin-27 (IL-27) as a sepsis diagnostic biomarker in children. Here we assess IL-27 as a sepsis diagnostic biomarker in critically ill adults with systemic inflammatory response syndrome and sepsis.. IL-27 and procalcitonin (PCT) were measured from plasma samples in three groups: no sepsis (n = 78), pulmonary source of sepsis (n = 66), and non-pulmonary source of sepsis (n = 43). Receiver operating characteristic curves and classification and regression tree methodology were used to evaluate biomarker performance.. IL-27 did not discriminate effectively between sepsis and sterile systemic inflammatory response syndrome in unselected patients. The highest area under the curve (AUC) was 0.70 (95% C.I. 0.60 - 0.80) for IL-27 in subjects with a non-pulmonary source of sepsis. A decision tree incorporating IL-27, PCT, and age had an AUC of 0.79 (0.71-0.87) in subjects with a non-pulmonary source of sepsis. Compared to children with sepsis, adults with sepsis express less IL-27.. IL-27 performed overall poorly in this cohort as a sepsis diagnostic biomarker. Combining IL-27, PCT, and age reasonably estimated the risk of sepsis in subjects with a non-pulmonary source of sepsis. IL-27 may be a more reliable sepsis diagnostic biomarker in children than in adults.

Topics: Age Factors; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Decision Trees; Diagnosis, Differential; Female; Humans; Interleukin-27; Male; Middle Aged; Protein Precursors; Respiratory Tract Infections; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

Accurate diagnosis of sepsis is difficult in patients post burn due to the large inflammatory response produced by the major insult. We aimed to estimate the values of serum N-terminal pro-B-type natriuretic peptide and procalcitonin and the changes in hemodynamic variables as markers of sepsis in critically ill burn patients.. Prospective, observational study.. A quaternary-level university-affiliated ICU.. Fifty-four patients with burns to total body surface area of greater than or equal to 15%, intubated with no previous cardiovascular comorbidities, were enrolled.. At admission, a FloTrac/Vigileo system was attached and daily blood samples taken from the arterial catheter. Infection surveillance was carried out daily with patients classified as septic/nonseptic according to American Burns Consensus criteria.. N-terminal pro-B-type natriuretic peptide, procalcitonin, and waveform analysis of changes in stroke volume index and systemic vascular resistance index were measured within the first 24 hours after burn and daily thereafter for the length of the ICU stay or until their first episode of sepsis. Prevalences of stroke volume variation less than 12% (normovolemia) with hypotension (systolic blood pressure < 90 mm Hg) were recorded. Patients with sepsis differed significantly from "no sepsis" for N-terminal pro-B-type natriuretic peptide, systemic vascular resistance index, and stroke volume index on days 3-7. Procalcitonin did not differ between sepsis and "no sepsis" except for day 3. Area under the receiver operating characteristic curves showed excellent discriminative power for B-type natriuretic peptide (p = 0.001; 95% CI, 0.99-1.00), systemic vascular resistance index (p < 0.001; 95% CI, 0.97-0.99), and stroke volume index (p < 0.01; 95% CI, 0.96-0.99) in predicting sepsis but not for procalcitonin (not significant; 95% CI, 0.29-0.46). A chi-square crosstab found that there was no relationship between hypotension with normovolemia (stroke volume variation < 12%) and sepsis.. Serum N-terminal pro-B-type natriuretic peptide levels and certain hemodynamic changes can be used as an early indicator of sepsis in patients with burn injury. Procalcitonin did not assist in the early diagnosis of sepsis.

Topics: Adolescent; Adult; Biomarkers; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Hemodynamics; Hospital Mortality; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Young Adult

Infections in critically ill patients continue to impose diagnostic and therapeutic challenges. We seek to investigate the utility of proadrenomedullin and procalcitonin as diagnostic and prognostic biomarkers in febrile critically ill patients with cancer and compare their performance with that of C-reactive protein.. Single-center prospective cohort study.. Tertiary care, academic, university hospital.. One hundred fourteen critically ill patients with cancer with fever.. None.. Blood samples were withdrawn on the day of fever onset and 4 to 7 days thereafter, and the serum proadrenomedullin, procalcitonin, and C-reactive protein levels were measured using the Kryptor technology afterward. Of the 114 adult patients, 27 had bloodstream infections, 36 had localized infections, and the remaining had no infections. The area under the receiver operating characteristic curve for bloodstream infection diagnosis was significantly greater for proadrenomedullin (0.70; 95% CI, 0.59-0.82) and procalcitonin (0.71; 95% CI, 0.60-0.83) compared with C-reactive protein (0.53; 95% CI, 0.39-0.66) (p = 0.021 and p = 0.003, respectively). Receiver operating characteristic analysis also showed that proadrenomedullin (p = 0.005) and procalcitonin (p = 0.009) each had a better performance than C-reactive protein in predicting patients' mortality within 2 months after their fever onset. Regarding patients' response to antimicrobial therapy, proadrenomedullin, procalcitonin, and C-reactive protein levels all significantly decreased from baseline to follow-up in responders (p ≤ 0.002), whereas only proadrenomedullin level significantly increased in nonresponders (p < 0.0001). In patients with documented infections, proadrenomedullin (0.81; 95% CI, 0.71-0.92) and procalcitonin (0.73; 95% CI, 0.60-0.85) each had a greater area under the curve compared with C-reactive protein (0.59; 95% CI, 0.45-0.73) as for as predicting response (p = 0.004 and p = 0.043, respectively). However, for all febrile patients, proadrenomedullin had a significantly greater area under the curve for predicting favorable response than procalcitonin (p < 0.0001).. In critically ill patients with cancer, proadrenomedullin and procalcitonin both have a promising role in predicting bloodstream infections in a manner more helpful than C-reactive protein. These two biomarkers were superior to C-reactive protein in the prognostic analysis of response to antimicrobial therapy for those patients with documented infections. However, proadrenomedullin was superior to procalcitonin in predicting response in all febrile patients and was unique in showing increased levels among nonresponders.

Topics: Academic Medical Centers; Adrenomedullin; Adult; Aged; Aged, 80 and over; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Middle Aged; Neoplasms; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sepsis

To facilitate the clinical diagnosis of ventilator-associated pneumonia (VAP) in the ICU, the Clinical Pulmonary Infection Score (CPIS) has been proposed but has shown a low diagnostic performance in subsequent studies. We propose a new score based on procalcitonin level and chest echography with the aim of improving VAP diagnosis: the Chest Echography and Procalcitonin Pulmonary Infection Score (CEPPIS).. This retrospective pilot study recruited patients admitted to the Intensive Care Unit of the Emergency Department, Careggi University Hospital (Florence, Italy), from January 2009 to December 2011. Patients were retrospectively divided into a microbiologically confirmed VAP group or a control group based on diagnosis of VAP and positive tracheal aspirate culture.. A total of 221 patients were included, with 113 in the microbiologically confirmed VAP group and 108 in the control group. A CEPPIS > 5 retrospectively fixed was significantly better in predicting VAP (OR, 23.78; sensitivity, 80.5%; specificity, 85.2%) than a CPIS > 6 (OR, 3.309; sensitivity, 39.8%; specificity, 83.3%). The receiver operating characteristic area under the curve analysis also showed a significantly higher diagnostic value for CEPPIS > 5 than CPIS > 6 (0.829 vs 0.616, respectively; P < .0001).. In this pilot, exploratory analysis, CEPPIS is effective in predicting VAP. Prospective validation is needed to confirm the potential value of this score to facilitate VAP diagnosis.

Topics: Aged; Analysis of Variance; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Critical Care; Critical Illness; Female; Hospital Mortality; Humans; Intensive Care Units; Italy; Logistic Models; Male; Middle Aged; Pilot Projects; Pneumonia, Ventilator-Associated; Predictive Value of Tests; Prognosis; Protein Precursors; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis; Ultrasonography, Doppler

The aim of this study was to investigate the diagnostic utility of plasma neutrophil gelatinase-associated lipocalin (NGAL) as an early objective biomarker to predict acute kidney injury (AKI) in critically ill patients with suspected sepsis, for whom procalcitonin (PCT) was used for the diagnosis and staging of sepsis.. Plasma NGAL was measured using the Triage NGAL Test (Alere, Inc., San Diego, CA, USA) in 231 samples obtained from patients with suspected sepsis. The results of NGAL were compared with those of Elecsys BRAHMS PCT (Roche Diagnostics, Basel, Switzerland). Renal failure was assessed using the renal subscore of Sepsis-related Organ Failure Assessment (SOFA) score. AKI was defined according to the Acute Kidney Injury Network criteria.. The concentrations of plasma NGAL were significantly different according to the five groups of PCT concentration (P<0.0001) and the renal subscore of SOFA score (P<0.0001). Plasma NGAL was significantly increased in the patients with AKI compared with those without AKI (416.5 ng/mL vs. 181.0 ng/mL, P=0.0223).. Plasma NGAL seems to be a highly sensitive and objective predictor of AKI in patients with sepsis. Plasma NGAL can be added for the diagnosis and staging of renal failure in sepsis.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Infant, Newborn; Lipocalin-2; Lipocalins; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Proto-Oncogene Proteins; Reagent Kits, Diagnostic; Sepsis; Severity of Illness Index

To analyze the variation of serum insulin levels in critically ill children and investigate the underlying mechanism and clinical significance to provide the basis for treatment.. Totally 332 critically ill children admitted in pediatric intensive care unit (PICU) of Hunan Children's Hospital from Nov., 2011 to April, 2012 were studied. The high insulin group (n = 332) was defined as insulin levels within 24 h > 11.1 mU/L and was divided into 2 groups: mildly elevated group (n = 194): 11.10 - 33.30 mU/L, increased three times group (n = 138): > 33.3 mU/L. Insulin, C-peptide and blood glucose were measured within 24 hours after admission, on day 3 and 7. Other results of inflammatory markers, lactate, cardiac enzymes, amylase, pancreatic ultrasound, hepatic and renal function as well as indicators related to severity and prognosis were recorded after admission.. The peak of insulin level was seen on day 1, then presented a downward trend and reached the normal level on day 7. The peaks of blood glucose and C-peptide level were seen on day 1 then declined, the levels on day 7 were still slightly higher than normal level. The insulin level on admission (41.47 ± 30.85) mU/L were positively correlated with lactic acid (2.29 ± 1.81) mmol/L and procalcitonin level (5.08 ± 6.70) ng/ml (r = 0.370, P = 0.000; r = 0.168, P = 0.002) (P < 0.01). The insulin level on admission in children with 1 organ failure (41.24 ± 22.60) mU/L or 2 or multiple organ failure (48.98 ± 22.17) mU/L was higher than that in children with non-organ failure (34.11 ± 29.84) mU/L (U = 1621.001, P = 0.000;U = 1300.000, P = 0.000) (P < 0.01). The insulin level on admission in death group (52.99 ± 32.34) mU/L was higher than that in survival group (32.85 ± 24.10) mU/L (U = 1585.000, P = 0.000) (P < 0.01). Ten cases in death group were complicated with pancreatic damage and the average insulin level on admission was (65.29 ± 50.53) mU/L.. The high insulin level was correlated with the degree of inflammatory response, ischemia and hypoxia. The high insulin level in critically ill children was relevant to the pancreatic damage, the severity of the disease, organ dysfunction, and evaluation of prognosis.

Topics: Adolescent; Blood Glucose; C-Peptide; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Infant, Newborn; Insulin; Intensive Care Units, Pediatric; Male; Multiple Organ Failure; Pancreas; Prognosis; Protein Precursors; Survival

Although absolute values for C-reactive protein (CRP) and procalcitonin (PCT) are well known to predict sepsis in the critically ill, it remains unclear how changes in CRP and PCT compare in predicting evolution of: infectious disease, invasiveness and severity (e.g. development of septic shock, organ failure and non-survival) in response to treatment. The current study attempts to clarify these aspects.. In 72 critically ill patients with new onset fever, CRP and PCT were measured on Day 0, 1, 2 and 7 after inclusion, and clinical courses were documented over a week with follow up to Day 28. Infection was microbiologically defined, while septic shock was defined as infection plus shock. The sequential organ failure assessment (SOFA) score was assessed.. From peak at Day 0-2 to Day 7, CRP decreased when (bloodstream) infection and septic shock (Day 0-2) resolved and increased when complications such as a new (bloodstream) infection or septic shock (Day 3-7) supervened. PCT decreased when septic shock resolved and increased when a new bloodstream infection or septic shock supervened. Increased or unchanged SOFA scores were best predicted by PCT increases and Day 7 PCT, in turn, was predictive for 28-day outcome.. The data, obtained during ICU-acquired fever and infections, suggest that CRP may be favoured over PCT courses in judging response to antibiotic treatment. PCT, however, may better indicate the risk of complications, such as bloodstream infection, septic shock, organ failure and mortality, and therefore might help deciding on safe discontinuation of antibiotics. The analysis may thus help interpreting current literature and design future studies on guiding antibiotic therapy in the ICU.

Topics: Adult; Aged; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Disease Progression; Female; Fever; Humans; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index; Survival Analysis

Topics: Acute Kidney Injury; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Hemofiltration; Humans; Membranes, Artificial; Protein Precursors; Sepsis; Veins

Topics: Aged; Aged, 80 and over; Autoimmune Diseases; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Kinetics; Male; Middle Aged; Protein Precursors; ROC Curve; Sensitivity and Specificity; Systemic Inflammatory Response Syndrome

We tested the hypothesis that higher mid-regional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations would be associated with increased prediction of mortality risk scores.. Prospective observational study set in two pediatric intensive care units (PICUs). Two-hundred-thirty-eight patients were included. MR-proADM, CT-proET-1, PCT and CRP levels were compared between children with PRISM III and PIM 2 > p75 (Group A; n = 33) and the rest (Group B; n = 205).. Median (range) MR-proADM levels were 1.39 nmol/L (0.52-12.67) in group A versus 0.54 (0.15-3.85) in group B (P < 0.001). CT-proET-1 levels were 172 pmol/L (27-500) versus 58 (4-447) (P < 0.001). PCT levels were 7.77 ng/mL (0.34-552.00) versus 0.28 (0.02-107.00) (P < 0.001). CRP levels were 6.23 mg/dL (0.08-28.25) versus 1.30 mg/dL (0.00-42.09) (P = 0.210). The area under the ROC curve (AUC) for the differentiation of group A and B was 0.87 (95% CI:0.81-0.821) for MR-proADM, 0.86 (95% CI:0.79-0.92) for CT-proET-1 and 0.84 (95% CI:0.74-0.94) for PCT. A MR-proADM > 0.79 nmol/L had 93% sensitivity and 76% specificity to differentiate groups, whereas a CT-proET-1 > 123 pmol/L had 77% sensitivity and 84% specificity, and a PCT concentration > 2.05 ng/mL had 80% sensitivity and specificity.. In critically ill children, high levels of MR-proADM, CT-proET-1 and PCT were associated with increased prediction of mortality risk scores. MR-proADM, CT-proET-1 and PCT concentrations higher than 0.80 nmol/L, 123 pmol/L and 2 ng/mL, respectively, could be used by clinicians to identify critically ill children at higher prediction of risk death scores.

Topics: Adrenomedullin; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Endothelin-1; Female; Humans; Male; Prospective Studies; Protein Precursors; Risk; Sensitivity and Specificity; Spain

To establish whether in critically ill patients without sepsis at intensive care unit (ICU) admission the percentage immature platelet fraction (IPF%) is a cellular marker predicting sepsis to verify a possible correlation between IPF% changes and manifest sepsis and describe the IPF% time course after ICU admission.. Prospective, observational 7-day study of 64 adult patients admitted to a general ICU at a University Hospital with no sepsis criteria. We measured daily IPF%, procalcitonin (PCT), C-reactive protein, platelets, white blood cell count and coagulation variables. Thirty-one patients with sepsis at ICU admission were studied as controls.. The only variable we tested at ICU admission that predicted sepsis was plasma IPF% (p < 0.001; >4.7 %: sensitivity 56.2 % IC 37.7-73.6; specificity 90.0 % IC 73.4-97.8). IPF% and PCT values were higher for the patients who had sepsis at admission and during the study than in patients in whom sepsis never developed (IPF%: p = 0.017; PCT: p = 0.030). Among the outcome variables, logistic regression was identified as the only variable related to the development of sepsis, IPF% (r = 0.51; p = 0.004). In patients who developed sepsis IPF% was inversely correlated with platelet count (r = -0.60; p < 0.001) and had high values before sepsis became manifest, decreasing significantly on the 2nd day thereafter.. In patients without sepsis at ICU admission IPF% increases before sepsis becomes manifest. Measuring IPF% through an easily available technology can therefore provide an early cellular marker predicting the development of sepsis.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Early Diagnosis; Female; Humans; Intensive Care Units; Leukocyte Count; Logistic Models; Male; Middle Aged; Platelet Count; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Thrombocytopenia

To determine the value of pancreatic stone protein in predicting sepsis-related postoperative complications and death in the ICU.. A prospective cohort study of postoperative patients admitted to the ICU. Blood samples for analysis were taken within 3 hours from admission to the ICU including pancreatic stone protein, white blood cell counts, C-reactive protein, interleukin-6, and procalcitonin. The Mannheim Peritonitis Index and Acute Physiology and Chronic Health Evaluation II clinical scores were also determined. Univariate and multivariate analyses were performed to determine the diagnostic accuracy and independent predictors of death in the ICU [Clinicaltrials.gov, NCT01465711].. An adult medical-surgical ICU in a teaching hospital in Germany.. Ninety-one consecutive postoperative patients with proven diagnosis of secondary peritonitis admitted to the ICU were included in the study from August 17, 2007, to February 8, 2010.. Peripheral vein blood sampling.. Univariate analysis demonstrated that pancreatic stone protein has the highest diagnostic accuracy for complications and is the best predictor for death in the ICU. Pancreatic stone protein had the highest overall efficacy in predicting death with an odds ratio of 4.0 vs. procalcitonin (odds ratio 3.2), interleukin-6 (odds ratio 2.8), C-reactive protein (odds ratio 1.3), and WBCs (odds ratio 1.4). By multivariate analysis, pancreatic stone protein was the only independent predictor of death.. In a population of patients with sepsis-related complications, serum-pancreatic stone protein levels demonstrate a high diagnostic accuracy to discriminate the severity of peritonitis and to predict death in the ICU. This test could be of value in the clinical diagnosis and therapeutic decision making in the ICU.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Critical Illness; Female; Germany; Humans; Intensive Care Units; Interleukin-6; Lithostathine; Male; Middle Aged; Peritonitis; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Survival Analysis

Fever suggests the presence of microbial infection in critically ill patients. The aim was to compare the role of old and new biomarkers in predicting absence or presence of microbial infection, its invasiveness and severity in critically ill patients with new onset fever.. We prospectively studied 101 patients in the intensive care unit with new onset fever (>38.3 °C). Routine infection parameters, lactate, procalcitonin (PCT), midregional pro-adrenomedullin (MR proADM), midregional pro-atrial natriuretic peptide (MR proANP) and copeptin (COP) were measured daily for three days after inclusion. Likelihood, invasiveness (by bloodstream infection, BSI) and severity of microbial infection were assessed by cultures, imaging techniques and clinical courses.. All patients had systemic inflammatory response syndrome; 45% had a probable or proven local infection and 12% a BSI, with 20 and 33% mortality in the ICU, respectively. Only peak PCT (cutoff 0.65 ng/mL at minimum) was of predictive value for all endpoints studied, i.e. BSI, septic shock and mortality (high risk infection) and infection without BSI, shock and mortality (low risk infection), at areas under the receiver operating characteristic curves varying between 0.67 (P = 0.003) and 0.72 (P < 0.001). In multivariable analysis, the combination of C-reactive protein and lactate best predicted high risk infection, followed by PCT. For low risk infection, PCT was the single best predictor.. In critically ill patients with new onset fever, plasma PCT as a single variable, among old and new biomarkers, best helps, to some extent, to predict ICU-acquired, high risk microbial infection when peaking above 0.65 ng/mL and low risk infection when peaking below 0.65 ng/mL.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fever of Unknown Origin; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Survival Analysis; Systemic Inflammatory Response Syndrome

Diagnosis of infection in patients receiving extracorporeal membrane oxygenation is challenging in clinical practice but represents a crucial aspect of the upgrading of therapeutic options. The aim of this study was to analyze the role of C-reactive protein and procalcitonin in the diagnosis of infection in patients requiring extracorporeal membrane oxygenation and to assess the difference between venovenous and venoarterial extracorporeal membrane oxygenation settings.. A case-control study was performed on 27 patients. Serum values of procalcitonin and C-reactive protein were analyzed according to the presence of infection.. Forty-eight percent of patients had infection. Gram-negative bacteria were the predominant pathogens, and Candida albicans was the most frequent isolated microorganism. Procalcitonin had an area under the curve of 0.681 (P = .0062) for the diagnosis of infection in the venoarterial extracorporeal membrane oxygenation group but failed to discriminate infection in the venovenous extracorporeal membrane oxygenation group (P = .14). The area under the curve of C-reactive protein was 0.707 (P < .001) in all patients receiving extracorporeal membrane oxygenation. In patients receiving venoarterial extracorporeal membrane oxygenation, procalcitonin had good accuracy with 1.89 ng/mL as the cutoff (sensitivity = 87.8%, specificity = 50%) and C-reactive protein with 97.70 mg/L as the cutoff (sensitivity = 85.3%, specificity = 41.6%). The procalcitonin and C-reactive protein combined assay had a sensitivity of 87.2% and specificity of 25.9%. Four variables were identified as statistically significant predictors of infection: procalcitonin and C-reactive protein combined assay (odds ratio, 1.184; P < .001), age (odds ratio, 0.980; P < .001), presence of infection before extracorporeal membrane oxygenation implantation (odds ratio, 1.782; P < .001), and duration of extracorporeal membrane oxygenation support (odds ratio, 1.056; P < .001).. Traditional and emerging inflammatory biomarkers, especially if compounded in the procalcitonin and C-reactive protein combined assay, can aid in the diagnosis of infection in patients undergoing venoarterial extracorporeal membrane oxygenation.

Topics: Adult; Aged; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Critical Illness; Extracorporeal Membrane Oxygenation; Female; Humans; Inflammation Mediators; Italy; Male; Middle Aged; Mycoses; Odds Ratio; Predictive Value of Tests; Prognosis; Protein Precursors; Sensitivity and Specificity; Time Factors

To identify predictors of bacteremia in critically ill patients, to evaluate the impact of blood cultures on the outcome, and to define conditions for breakthrough bacteremia despite concurrent antibiotic treatment.. A descriptive retrospective study was performed over a two-year period (2007-2008) in the medico-surgical Intensive Care Unit (ICU) of the San Giovanni Hospital in Bellinzona, Switzerland.. Forty-five out of 231 patients (19.5%) had positive blood cultures. Predictors of positive blood cultures were elevated procalcitonin levels (>2 µg/L, P<0.001), higher severity scores (Simplified Acute Physiology Score II>43, P=0.014; Sequential Organ Failure Assessment >4.0, P<0.001), and liver failure (P=0.028). Patients with bacteremia had longer hospital stays (31 vs 21 days, P=0.058), but their mortality was not different from patients without bacteremia. Fever (t>38.5°C) only showed a trend toward a higher rate of blood culture positivity (P=0.053). The rate of positive blood cultures was not affected by concurrent antibiotic therapy.. The prediction of positive blood culture results still remains a very difficult task. In our analysis, blood cultures were positive in 20% of ICU patients whose blood was cultured, and positive findings increased with elevated procalcitonin levels, liver failure, and higher severity scores. Blood cultures drawn >4 days after the start of antibiotic therapy and >5 days after surgery could detect pathogens responsible for a new infection complication.

Topics: Aged; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fever; Humans; Intensive Care Units; Length of Stay; Liver Failure; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Severity of Illness Index

The plasma level of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) has been shown to be helpful in identifying critically ill patients with infection. However, it remains unknown whether it can be used to predict prognosis in patients with severe sepsis. This study investigated whether various inflammatory mediators, including sTREM-1, could be used as reliable markers to predict the prognosis of patients receiving early goal-directed therapy (EGDT). We prospectively enrolled patients 18 years or older with severe sepsis from April 2009 to May 2010 at a 2,000-bed university hospital. Patients were eligible if the initial resuscitation according to EGDT protocol was immediately performed at the emergency department. Plasma sTREM-1, C-reactive protein, and procalcitonin concentrations were measured on days 0, 3, 7, and 14. Soluble TREM-1 concentrations were significantly higher at admission and pre-EGDT in nonsurvivors (n = 16) than in survivors (n = 47) (514.1 pg/mL [interquartile range, 412.7-1,749.5 pg/mL] vs. 182.4 pg/mL [interquartile range, 54.3-327.0 pg/mL]; P = 0.001). Procalcitonin and C-reactive protein levels did not significantly differ, whereas central venous oxygen saturation and lactate levels at admission were significantly different between the two groups. The only sTREM-1 level remained significantly higher in nonsurvivors until death. On multivariate regression analysis, log(sTREM-1) (P = 0.028), central venous oxygen saturation (P = 0.022), and Simplified Acute Physiology Score II (P = 0.048) values at admission were independently significant. These results suggest that plasma sTREM-1 level at admission could be used as a marker to identify patients with a poor prognosis despite complete initial resuscitation in severe sepsis.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Emergency Service, Hospital; Female; Humans; Male; Membrane Glycoproteins; Middle Aged; Monitoring, Physiologic; Prognosis; Protein Precursors; Receptors, Immunologic; Resuscitation; Sepsis; Severity of Illness Index; Triggering Receptor Expressed on Myeloid Cells-1

During the 2009 influenza A H1N1 pandemic, it became difficult to differentiate viral infections from other conditions in patients admitted to the intensive care unit. We sought to evaluate the behavior and diagnostic utility of procalcitonin, C-reactive protein and four other molecules in patients with suspected 2009 Influenza A H1N1 infection.. The serum levels of procalcitonin, C-reactive protein, tumor necrosis factor α, interferon γ, interleukin 1β, and interleukin 10 were tested on admission and on days 3, 5, and 7 in 35 patients with suspected 2009 H1N1 infection who were admitted to two ICUs.. Twelve patients had confirmed 2009 influenza A H1N1 infections, 6 had seasonal influenza infections, and 17 patients had negative swabs. The procalcitonin levels at inclusion and on day 3, and the C-reactive protein levels on day 3 were higher among subjects with 2009 influenza A H1N1 infections. The baseline levels of interleukin 1b were higher among the 2009 influenza A H1N1 patients compared with the other groups. The C-reactive protein levels on days 3, 5, and 7 and procalcitonin on days 5 and 7 were greater in non-surviving patients.. Higher levels of procalcitonin, C-reactive protein and interleukin-1β might occur in critically ill patients who had a 2009 H1N1 infection. Neither procalcitonin nor CRP were useful in discriminating severe 2009 H1N1 pneumonia. Higher levels of CRP and procalcitonin appeared to identify patients with worse outcomes.

Topics: Adolescent; Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Diagnosis, Differential; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Interleukin-1beta; Male; Prospective Studies; Protein Precursors; Real-Time Polymerase Chain Reaction; Respiratory Distress Syndrome; Virus Diseases; Young Adult

Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis, the assessment of infection in critically ill patients is often a challenge for clinicians. In this setting, simple biomarkers, especially when used in combination, could prove useful.. To determine the usefulness of combination biomarkers to diagnose sepsis.. Three hundred consecutive patients were enrolled to construct a biologic score that was next validated in an independent prospective cohort of 79 critically ill patients from another center.. Plasma concentrations of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and procalcitonin (PCT) were assayed, and the expression of the high-affinity immunoglobulin-Fc fragment receptor I (FcγRI) CD64 on neutrophils (polymorphonuclear [PMN] CD64 index) in flow cytometry was measured. A "bioscore" combining these biomarkers was constructed. Serum concentrations of PCT and sTREM-1 and the PMN CD64 index were higher in patients with sepsis compared with all others (P < 0.001 for the three markers). These biomarkers were all independent predictors of infection, the best receiver-operating characteristic curve being obtained for the PMN CD64 index. The performance of the bioscore, better than that of each individual biomarker, was externally confirmed in the validation cohort.. This prospective study, including inceptive and validation cohorts of unselected intensive care unit patients, demonstrates the high performance of a bioscore combining the PMN CD64 index together with PCT and sTREM-1 serum levels in diagnosing sepsis in the critically ill patient.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Logistic Models; Membrane Glycoproteins; Myeloid Cells; Predictive Value of Tests; Prospective Studies; Protein Precursors; Receptors, IgG; Receptors, Immunologic; ROC Curve; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

The utility of procalcitonin for the diagnosis of infection in the critical care setting has been extensively investigated with conflicting results. Herein, we report procalcitonin values relative to baseline patient characteristics, presence of shock, intensive care unit time course, infectious status, and Gram stain of infecting organism.. Prospective, multicenter, observational study of critically ill patients admitted to intensive care unit for >24 hrs.. Three tertiary care intensive care units.. All consenting patients admitted to three mixed medical-surgical intensive care units. Patients who had elective surgery, overdoses, and who were expected to stay <24 hrs were excluded.. Patients were followed prospectively to ascertain the presence of prevalent (present at admission) or incident (developed during admission) infections and clinical outcomes. Procalcitonin levels were measured daily for 10 days and were analyzed as a function of the underlying patient characteristics, presence of shock, time of infection, and pathogen isolated.. Five hundred ninety-eight patients were enrolled. Medical and surgical infected cohorts had similar baseline procalcitonin values (3.0 [0.7-15.3] vs. 3.7 [0.6-9.8], p=.68) and peak procalcitonin (4.5 [1.0-22.9] vs. 5.0 [0.9-16.0], p=.91). Infected patients were sicker than their noninfected counterparts (Acute Physiology and Chronic Health Evaluation II 22.9 vs. 19.3, p<.001); those with infection at admission had a trend toward higher peak procalcitonin values than did those whose infection developed in the intensive care unit (4.9 vs. 1.4, p=.06). The presence of shock was significantly associated with elevations in procalcitonin in cohorts who were and were not infected (both groups p<.003 on days 1-5).. Procalcitonin dynamics were similar between surgical and medical cohorts. Shock had an association with higher procalcitonin values independent of the presence of infection. Trends in differences in procalcitonin values were seen in patients who had incident vs. prevalent infections.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Infections; Intensive Care Units; Length of Stay; Male; Middle Aged; Prospective Studies; Protein Precursors; Shock; Time Factors

Procalcitonin (PCT), the prohormone of calcitonin, has an early and highly specific increase in response to systemic bacterial infection. The objectives of this study were to determine the natural history of PCT for patients with critical illness and trauma, the utility of PCT as a marker of sepsis versus systemic inflammatory response syndrome (SIRS), and the association of PCT level with mortality.. PCT assays were done on eligible patients with trauma admitted to the trauma intensive care unit (ICU) of a Level I trauma center from June 2009 to June 2010, at hours 0, 6, 12, 24, and daily until discharge from ICU or death. Patients were retrospectively diagnosed with SIRS or sepsis by researchers blinded to PCT results.. A total of 856 PCT levels from 102 patients were analyzed, with mean age of 49 years, 63% male, 89% blunt trauma, mean Injury Severity Score of 21, and hospital mortality of 13%. PCT concentration for patients with sepsis, SIRS, and neither were evaluated. Mean PCT levels were higher for patients with sepsis versus SIRS (p < 0.0001). Patients with a PCT concentration of 5 ng/mL or higher had an increased mortality when compared with those with a PCT of less than 5 ng/mL in a univariate analysis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9; p = 0.04). In a multivariate logistic analysis, PCT was found to be the only significant predictor for sepsis (odds ratio, 2.37; 95% confidence interval,1.23-4.61, p = 0.01).. PCT levels are significantly higher in ICU patients with trauma and sepsis and may help differentiate sepsis from SIRS in critical illness. An elevated PCT level was associated with increased mortality.

Topics: Adult; Aged; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Confidence Intervals; Critical Care; Critical Illness; Diagnosis, Differential; Disease Progression; Female; Hospital Mortality; Humans; Injury Severity Score; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; ROC Curve; Sensitivity and Specificity; Sepsis; Survival Rate; Systemic Inflammatory Response Syndrome; Trauma Centers; Wounds, Nonpenetrating

The aim of our study was to evaluate the prognostic value of MR-proADM and PCT levels in febrile patients in the ED in comparison with a disease severity index score, the APACHE II score. We also evaluated the ability of MR-proADM and PCT to predict hospitalization.. This was an observational, multicentric study. We enrolled 128 patients referred to the ED with high fever and a suspicion of severe infection such as sepsis, lower respiratory tract infections, urinary tract infections, gastrointestinal infections, soft tissue infections, central nervous system infections, or osteomyelitis. The APACHE II score was calculated for each patient.. MR-proADM median values in controls were 0.5 nmol/l as compared with 0.85 nmol/l in patients (P < 0.0001), while PCT values in controls were 0.06 ng/ml versus 0.56 ng/ml in patients (P < 0.0001). In all patients there was a statistically significant stepwise increase in MR-proADM levels in accordance with PCT values (P < 0.0001). MR-proADM and PCT levels were significantly increased in accordance with the Apache II quartiles (P < 0.0001 and P = 0.0012 respectively).In the respiratory infections, urinary infections, and sepsis-septic shock groups we found a correlation between the Apache II and MR-proADM respectively and MR-proADM and PCT respectively. We evaluated the ability of MR-proADM and PCT to predict hospitalization in patients admitted to our emergency departments complaining of fever. MR-proADM alone had an AUC of 0.694, while PCT alone had an AUC of 0.763. The combined use of PCT and MR-proADM instead showed an AUC of 0.79.. The present study highlights the way in which MR-proADM and PCT may be helpful to the febrile patient's care in the ED. Our data support the prognostic role of MR-proADM and PCT in that setting, as demonstrated by the correlation with the APACHE II score. The combined use of the two biomarkers can predict a subsequent hospitalization of febrile patients. The rational use of these two molecules could lead to several advantages, such as faster diagnosis, more accurate risk stratification, and optimization of the treatment, with consequent benefit to the patient and considerably reduced costs.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Aged, 80 and over; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Emergency Medical Services; Female; Fever; Humans; Male; Middle Aged; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index; Young Adult

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Male; Protein Precursors

Procalcitonin (PCT) has emerged as a valuable marker of sepsis. The potential role of PCT in diagnosis and therapy monitoring of intravascular catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) is still unclear and was evaluated.. Forty-six patients were included in the study, provided they were free of infection upon admission and presented the first episode of suspected CRBSI during their ICU stay. Patients who had developed any other infection were excluded. PCT was measured daily during the ICU hospitalization. Primary endpoint was proven CRBSI. Therapy monitoring as according to infection control was also evaluated.. Among the 46 patients, 26 were diagnosed with CRBSI. Median PCT on the day of infection suspicion (D0) was 7.70 and 0.10 ng/ml for patients with and without proven CRBSI, respectively (p < 0.001). The area under the curve (AUC) for PCT was 0.990 (95% CI; 0.972 - 1.000), whereas a cut-off value of 0.70 ng/ml provided sensitivity and specificity of 92.3 and 100% respectively. In contrast, the AUC for white blood cells (WBC) was 0.539 (95% CI; 0.369 - 0.709), and for C-reactive protein (CRP), 0.603 (95% CI; 0.438 - 0.768). PCT was the best predictor of proven infection. Moreover, an increase >0.20 ng/ml of PCT between the D0 and any of the 4 preceding days was associated with a positive predictive value exceeding 96%. PCT concentrations from the D2 to D6 after suspected infection tended to decrease in controlled patients, whereas remained stable in non-controlled subjects. A PCT concentration exceeding 1.5 ng/ml during D3 was associated with lack of responsiveness to therapy (p = 0.028).. We suggest that PCT could be a helpful diagnostic and prognostic marker of CRBSI in critically ill patients. Both absolute values and variations should be considered.

Topics: Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Catheter-Related Infections; Cohort Studies; Critical Illness; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children.. Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis.. Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone.. Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children. Additional studies will be required to test further the diagnostic performance of IL-27. The microarray data reported in this article have been deposited in the Gene Expression Omnibus under accession number GSE4607.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Critical Illness; Female; Gene Expression; Humans; Infant; Interleukins; Male; Microarray Analysis; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Timely diagnosis and prognostic assessment of ventilator-associated pneumonia remain major challenges in critical care.. To explore the value of soluble triggering receptor expressed on myeloid cells 1, procalcitonin, and the Clinical Pulmonary Infection Score in the diagnosis and prognostic assessment of ventilator-associated pneumonia.. For 92 patients, bronchoalveolar lavage fluid was cultured for detection of microorganisms, serum levels of the receptor and procalcitonin and levels of the receptor in exhaled ventilator condensate were measured, and the Clinical Pulmonary Infection Score was calculated.. On the day of diagnosis, patients who had pneumonia had higher serum levels of the receptor, procalcitonin, and C-reactive protein; higher white blood cell counts; and higher pulmonary infection and Sequential Organ Failure Assessment scores than did patients without pneumonia. White blood cell count (odds ratio, 1.118; 95% CI, 1.139-1.204) and serum levels of the receptor (odds ratio, 1.002; 95% CI, 1.000-1.005) may be risk factors for VAP. Serum levels of the receptor plus the pulmonary infection score were the most reliable for diagnosis; the area under the receiver operating characteristic curve was 0.972 (95% CI, 0.945-0.999), sensitivity was 0.875, and specificity was 0.95. For 28-day survival, procalcitonin level combined with pulmonary infection score was the most reliable for prognostic assessment (area under the curve, 0.848; 95% CI, 0.672-1.025).. In patients with ventilator-associated pneumonia, serum levels of the receptor plus the pulmonary infection score are useful for diagnosis, and procalcitonin levels plus the pulmonary infection score are useful for prognostic assessment.

Topics: Breath Tests; Bronchoalveolar Lavage Fluid; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Leukocyte Count; Male; Membrane Glycoproteins; Middle Aged; Multivariate Analysis; Odds Ratio; Pneumonia, Ventilator-Associated; Prognosis; Protein Precursors; Receptors, Immunologic; Risk Factors; ROC Curve; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Triggering Receptor Expressed on Myeloid Cells-1

The purpose of the study was to know the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) in critically ill patients with H1N1 influenza A virus pneumonia and to compare levels of these inflammatory mediators with patients with acute community-acquired bacterial pneumonia.. An observational study in a mixed intensive care unit (ICU) at a general university hospital was performed. All consecutive patients admitted to the ICU with a diagnosis of severe acute community-acquired pneumonia from September 2009 to December 2009 were included. Viral (H1N1 influenza A) and bacterial microbiological diagnoses were done in every patient. At admission, demographics, comorbidities, Simplified Acute Physiology Score, Sequential Organ Failure Assessment, Lung Injury Score, and Pao(2)/Fio(2) were recorded. At admission and after 24, 48, and 120 hours, WBC, CRP, and PCT levels were obtained. Finally, hospital and ICU length of stay and mortality were recorded.. No differences in CRP or WBC were found between H1N1-positive patients and H1N1-negative patients (patients with acute community-acquired bacterial pneumonia). Procalcitonin levels at admission were lower in H1N1-positive patients (PCT = 0.4 [0.1-6.1] ng/mL) than in the H1N1-negative patients (24.8 [13.1-34.5] ng/mL). Procalcitonin significantly decreased with time but remained lower in the H1N1-positive group at all measurements (P < .05 for all comparisons).. Among patients admitted to the ICU with pneumonia, the PCT level could help identify H1N1 influenza A virus pneumonia and thus enable earlier antiviral therapy.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Critical Illness; Female; Hospitals, University; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Intensive Care Units; Length of Stay; Leukocyte Count; Male; Middle Aged; Pilot Projects; Pneumonia, Bacterial; Pneumonia, Viral; Prospective Studies; Protein Precursors

The expression of Fc receptors for IgG (FcγRs) on neutrophils, including CD16, CD32 and CD64, may be modulated in response to sepsis. We investigated the expression of FcγRs on neutrophils and procalcitonin (PCT) as biomarkers of sepsis among critically ill patients.. This prospective study was conducted in a 24-bed respiratory intensive care unit between July 2007 and June 2008. Critically ill patients requiring mechanical ventilation were enrolled and categorized into three groups: those with systemic inflammatory response syndrome (SIRS), those with severe sepsis and those with septic shock. Expression of FcγRs on neutrophils was quantitatively measured by flow cytometry immediately after enrolment of the patient. Serum PCT levels were also measured. Receiver operating characteristic (ROC) curves were used to evaluate the performance of FcγR expression and PCT as biomarkers of sepsis.. Sixty-six patients were enrolled, including 11 with SIRS, 31 with severe sepsis and 24 with septic shock. Nineteen healthy volunteers served as normal controls. CD64 was upregulated, CD16 was downregulated and CD32 remained unchanged during sepsis. CD64 expression and the ratio of CD64/CD16 increased significantly with the severity of sepsis. However, serum PCT levels were not significantly different between SIRS and severe sepsis patients. CD64, CD64/CD16 and PCT all significantly predicted sepsis, septic shock and bacteraemia. As assessed using ROC curves, CD64 was better than PCT for differentiating SIRS from severe sepsis and septic shock. CD64 and CD64/CD16 were associated with mortality.. CD64 and CD16 were differentially modulated by sepsis. CD64, CD64/CD16 and PCT may be biomarkers of sepsis. CD64 was better than PCT for identifying patients who required treatment with antibiotics.

Topics: Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Chronic Disease; Comorbidity; Critical Illness; Female; Flow Cytometry; Humans; Male; Middle Aged; Neutrophils; Prospective Studies; Protein Precursors; Receptors, IgG; Sepsis; Severity of Illness Index

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Fungemia; Humans; Protein Precursors

Recognizing infection is crucial in immunocompromised patients with organ dysfunction. Our objective was to assess the diagnostic accuracy of procalcitonin (PCT) in critically ill immunocompromised patients.. This prospective, observational study included patients with suspected sepsis. Patients were classified into one of three diagnostic groups: no infection, bacterial sepsis, and nonbacterial sepsis.. We included 119 patients with a median age of 54 years (interquartile range [IQR], 42-68 years). The general severity (SAPSII) and organ dysfunction (LOD) scores on day 1 were 45 (35-62.7) and 4 (2-6), respectively, and overall hospital mortality was 32.8%. Causes of immunodepression were hematological disorders (64 patients, 53.8%), HIV infection (31 patients, 26%), and solid cancers (26 patients, 21.8%). Bacterial sepsis was diagnosed in 58 patients and nonbacterial infections in nine patients (7.6%); 52 patients (43.7%) had no infection. PCT concentrations on the first ICU day were higher in the group with bacterial sepsis (4.42 [1.60-22.14] vs. 0.26 [0.09-1.26] ng/ml in patients without bacterial infection, P < 0.0001). PCT concentrations on day 1 that were > 0.5 ng/ml had 100% sensitivity but only 63% specificity for diagnosing bacterial sepsis. The area under the receiver operating characteristic (ROC) curve was 0.851 (0.78-0.92). In multivariate analyses, PCT concentrations > 0.5 ng/ml on day 1 independently predicted bacterial sepsis (odds ratio, 8.6; 95% confidence interval, 2.53-29.3; P = 0.0006). PCT concentrations were not significantly correlated with hospital mortality.. Despite limited specificity in critically ill immunocompromised patients, PCT concentrations may help to rule out bacterial infection.

Topics: Adult; Aged; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Immunocompromised Host; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index

Multiorgan dysfunction syndrome represents a continuum of cumulative organ dysfunction from very mildly altered function to total and, rarely, irreversible organ failure and is the major cause of death in the intensive care unit (ICU). The terms multiple organ failure syndrome (MOFS), multiple organ system failure (MOSF), and multiple organ failure (MOF) have since been used to describe this syndrome. Infections were initially thought to be the main cause of multiorgan dysfunction; however, other insults, such as severe trauma, burn injuries, and noninfectious inflammatory diseases may precipitate a similar condition. In 2001, several North American and European intensive care societies revisited the definitions for sepsis and related conditions. Additional criteria indicative of physiological derangements were added to the traditional systemic inflammatory response syndrome (SIRS) criteria, including clinical abnormalities (altered mental status, ileus) and biochemical evidence of a sepsis response [procalcitonin (PCT), C-reactive protein (CRP), creatinine, or cytokine levels]. The use of organ failure scores to describe organ dysfunction in ICU patients was encouraged. The pulmonary, cardiovascular, renal, hepatic, hematologic, and central nervous systems are the organs most commonly considered when describing organ dysfunction/failure in the ICU. Scoring systems for organ dysfunction/failure were designed primarily as descriptive tools, aimed at establishing standardized definitions to stratify and compare patients in the ICU in terms of morbidity rather than mortality. Sequential evaluation of organ dysfunction during the ICU stay may track disease progression and may be useful prognostically. We discuss the various scoring systems developed over the past 2 decades and present a rational approach to their role in assessing and following critically ill patients.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Critical Illness; Cytokines; Disease Progression; Humans; Intensive Care Units; Multiple Organ Failure; Prognosis; Protein Precursors; Sepsis

To develop a scoring method for quantifying nutrition risk in the intensive care unit (ICU).. A prospective, observational study of patients expected to stay > 24 hours. We collected data for key variables considered for inclusion in the score which included: age, baseline APACHE II, baseline SOFA score, number of comorbidities, days from hospital admission to ICU admission, Body Mass Index (BMI) < 20, estimated % oral intake in the week prior, weight loss in the last 3 months and serum interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) levels. Approximate quintiles of each variable were assigned points based on the strength of their association with 28 day mortality.. A total of 597 patients were enrolled in this study. Based on the statistical significance in the multivariable model, the final score used all candidate variables except BMI, CRP, PCT, estimated percentage oral intake and weight loss. As the score increased, so did mortality rate and duration of mechanical ventilation. Logistic regression demonstrated that nutritional adequacy modifies the association between the score and 28 day mortality (p = 0.01).. This scoring algorithm may be helpful in identifying critically ill patients most likely to benefit from aggressive nutrition therapy.

Topics: Aged; APACHE; Body Mass Index; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chi-Square Distribution; Critical Illness; Eating; Female; Humans; Interleukin-6; Length of Stay; Logistic Models; Male; Middle Aged; Nutrition Assessment; Nutrition Therapy; Nutritional Status; Prospective Studies; Protein Precursors; Risk Assessment; Statistics, Nonparametric; Weight Loss

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

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

Topics: Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Drug Monitoring; Female; Humans; Intensive Care Units; Male; Postoperative Complications; Protein Precursors

This study investigated the effects of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on gut barrier function in critically ill surgical patients.. A prospective observational cohort study on patients with severe acute pancreatitis or abdominal sepsis admitted to an intensive care or high-dependency unit. Intra-abdominal pressure (IAP) and plasma levels of immunoglobulin G (IgG) and IgM antiendotoxin core antibodies (EndoCAb) and procalcitonin (ProCT) were measured serially.. Among 32 recruited patients, 24 (75%) and 8 patients (25%) developed IAH and ACS, respectively. The state of ACS was associated with significant reductions in plasma IgG EndoCAb (P = 0.015) and IgM EndoCAb (P = 0.016) and higher concentrations of plasma ProCT (P = 0.056) compared with absence of ACS. Resolution of IAH and ACS was associated with significant recovery of plasma IgG EndoCAb (P = 0.003 and P = 0.009, respectively) and IgM EndoCAb (P = 0.002 and P = 0.003, respectively) and reduction in plasma ProCT concentration (P = 0.049 and P = 0.019, respectively). Negative correlations were observed between IAP and plasma IgG EndoCAb (P = 0.003) and IgM EndoCAb (P = 0.002).. Intra-abdominal hypertension and ACS are associated with significantly higher endotoxin exposure and ProCT concentrations, suggestive of gut barrier dysfunction. Resolution of IAH and ACS is associated with evidence for recovery of gut barrier function.

Topics: Abdominal Cavity; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Compartment Syndromes; Critical Illness; Female; Humans; Hypertension; Intestinal Mucosa; Male; Middle Aged; Prospective Studies; Protein Precursors

Established biomarkers for the diagnosis of sepsis are procalcitonin, interleukin 6, and C-reactive protein. Although sepsis evokes changes of coagulation and fibrinolysis, it is unknown whether thromboelastometry can detect these alterations. We investigated whether thromboelastometry variables are suitable as biomarkers for severe sepsis in critically ill adults.. In the observational cohort study, blood samples were obtained from patients on the day of diagnosis of severe sepsis (n = 56) and from postoperative patients (n = 52), and clotting time, clot formation time, maximum clot firmness, alpha angle, and lysis index were measured with thromboelastometry. In addition, procalcitonin, interleukin 6, and C-reactive protein levels were determined. For comparison of biomarkers, receiver operating characteristic (ROC) curves were used, and the optimal cut-offs and odds ratios were calculated.. In comparison with postoperative controls, patients with sepsis showed an increase in lysis index (97% ± 0.3 versus 92 ± 0.5; P < 0.001; mean and SEM) and procalcitonin (2.5 ng/ml ± 0.5 versus 30.6 ± 8.7; P < 0.001). Clot-formation time, alpha angle, maximum clot firmness, as well as interleukin 6 and C-reactive protein concentrations were not different between groups; clotting time was slightly prolonged. ROC analysis demonstrated an area under the curve (AUC) of 0.901 (CI 0.838-0.964) for the lysis index, and 0.756 (CI 0.666-0.846) for procalcitonin. The calculated cut-off for the lysis index was > 96.5%, resulting in a sensitivity of 84.2%, and a specificity of 94.2%, with an odds ratio of 85.3 (CI 21.7-334.5).. The thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein. The results also demonstrate that early involvement of the hemostatic system is a common event in severe sepsis.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Critical Illness; Female; Hemolysis; Humans; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis; Thrombelastography; Up-Regulation

Chromogranin A (CGA), a stress marker released with catecholamines by the adrenal medulla, has never been associated with acute inflammation in critically ill patients.. To determine evidence for a link between serum concentration of CGA, biomarkers of inflammation, and outcome inpatients admitted with or without the systemic inflammatory response syndrome (SIRS).. At admission, we measured in 53 patients and 14 healthy controls the serum concentrations of CGA,procalcitonin, and C-reactive protein. We also assessed the Simplified Acute Physiological Score (SAPS) in the patients.. Serum CGA concentrations were significantly increased in SIRS patients with a median value of 115 microg/L (68.0-202.8), when compared to healthy controls (PB0.001). In cases where infection was associated with SIRS, patients had the highest increase in CGA with a median value of 138.5 microg/L (65-222.3) (PB0.001). CGA concentrations positively correlated with inflammation markers (procalcitonin, C-reactive protein), but also with SAPS. Receiver operating characteristic (ROC) analysis showed that CGA is equivalent to SAPS as an indicator for 28-day mortality (area under curve (AUC) for both: 0.810).. Patients with CGA concentration superior to 71 microg/L have a significantly shorter survival. A Cox model confirmed that CGA and SAPS were independent predictors of outcome.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chromogranin A; Critical Illness; Female; Humans; Intensive Care Units; Male; Middle Aged; Patient Admission; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Severity of Illness Index; Survival Rate; Systemic Inflammatory Response Syndrome

The importance of postoperative procalcitonin (PCT) measurements for outcome prediction is currently controversial. Conflicting results have been obtained for patients after polytrauma, sepsis, peritonitis, or cardiac surgery and may result from incomplete adjustment for important confounders or from nonlinear PCT effects. We retrospectively analyzed the association of PCT concentration with postoperative mortality, morbidity, and length of stay in an unselected series of 220 consecutive patients who required postoperative intensive care unit therapy or surveillance. Biochemical markers were measured on the first day after intensive care unit admission. Results were adjusted for various confounding variables (Acute Physiology and Chronic Health Evaluation II score, underlying disease), and test accuracy was evaluated by receiver operating characteristic statistics. We found a significant nonlinear, logarithmic association between PCT concentration and outcome. After adjustment for relevant covariates, PCT was an independent determinant of mortality, combined mortality/morbidity, and postoperative hospital length of stay in survivors. At mortality analysis, the predictive power of PCT was superior to that of Acute Physiology and Chronic Health Evaluation II score and of IL-6 (optimal cutoff point, 1.44 ng/mL; sensitivity, 80.8%; specificity, 80.4%). The use of PCT was comparable to that of other prognostic markers when combined mortality/morbidity were examined. Our results suggest that PCT may deserve further testing as a prognostic tool in unselected, critically ill, surgical patients.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Models, Statistical; Postoperative Period; Protein Precursors; Retrospective Studies

Serial procalcitonin is reported to be useful to titrate duration of antibiotic therapy in the non critically ill patient with pneumonia. The aim of this study was to examine the relationship between antibiotic therapy and serial serum procalcitonin concentrations in a cohort of critically ill septic patients and examine for any differences between culture positive (CP) and culture negative (CN) sepsis. Seventy-five critically ill patients with suspected sepsis were enrolled in this prospective observational study. Serial procalcitonin and C-reactive protein assays were measured on days one, three, five, seven, 10 and 14. The mean duration of antibiotic therapy was similar in the two groups (10.4 +/- 5.1 (CP) vs. 8.4 +/- 5.1 (CN) days, P = 0.09). Serum procalcitonin concentrations were significantly higher at baseline in the CP than the CN group (14.9 +/- 22.9 vs. 6.8 +/- 21.5 ng/ml, P = 0.04). During the study period, serum concentrations of procalcitonin and C-reactive protein declined in both groups. Serum procalcitonin consistently remained higher in the CP group (P < 0.05) and did not return to normal values. In the CN group, procalcitonin concentrations fell below 0.5 only on day 10. There was no significant difference in C-reactive protein profile between the two groups. Four patients in the CP group (11%) had relapse of sepsis. The mean procalcitonins in the relapsed subgroup were lower than those in the remission subgroup (P = 0.02). Therapy for proven or presumed infections was associated with declining serum procalcitonin and C-reactive protein in critically ill septic patients. The marked variability and overlap in plasma profile of these markers between CP and CN sepsis makes it difficult to define a nadir plasma concentration at which one can recommend discontinuation of antibiotic therapy.

Topics: Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Recurrence; Sensitivity and Specificity; Sepsis; Time Factors

This purpose of this study was to determine if serum procalcitonin (PCT) concentration at the time of admission to the ICU is a predictor of all-cause short-term mortality.. This prospective cross-sectional study was conducted over a 16-month period with 86 consecutive critically ill patients. The semi-quantitative PCT-Q test was performed and APACHE II scores and C-reactive protein (CRP) concentrations were determined within 24 h of admission.. PCT-Q test value was a better predictor of all-cause short-term mortality than CRP value or APACHE II score. PCT > or = 10 ng/mL was highly and independently correlated with mortality. Use of PCT-Q > or = 10 ng/mL was superior to use of APACHE II > or = 25 or CRP > or = 10 mg/dL as a predictor of poor outcome.. A PCT-Q value > or = 10 ng/mL obtained at the time of admission to the ICU is a strong predictor of short-term mortality.

Topics: APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Demography; Female; Humans; Intensive Care Units; Male; Middle Aged; Patient Admission; Prognosis; Protein Precursors; ROC Curve; Sepsis; Survival Analysis; Time Factors; Treatment Outcome

The usefulness of procalcitonin (PCT) measurement in critically ill medical patients with suspected nosocomial infection is unclear. The aim of the study was to assess PCT value for the early diagnosis of bacterial nosocomial infection in selected critically ill patients.. An observational cohort study in a 15-bed intensive care unit was performed. Seventy patients with either proven (n = 47) or clinically suspected but not confirmed (n = 23) nosocomial infection were included. Procalcitonin measurements were obtained the day when the infection was suspected (D0) and at least one time within the 3 previous days (D-3 to D0). Patients with proven infection were compared to those without. The diagnostic value of PCT on D0 was determined through the construction of the corresponding receiver operating characteristic (ROC) curve. In addition, the predictive value of PCT variations preceding the clinical suspicion of infection was assessed.. PCT on D0 was the best predictor of proven infection in this population of ICU patients with a clinical suspicion of infection (AUROCC = 0.80; 95% CI, 0.68-0.91). Thus, a cut-off value of 0.44 ng/mL provides sensitivity and specificity of 65.2% and 83.0%, respectively. Procalcitonin variation between D-1 and D0 was calculated in 45 patients and was also found to be predictive of nosocomial infection (AUROCC = 0.89; 95% CI, 0.79-0.98) with a 100% positive predictive value if the +0.26 ng/mL threshold value was applied. Comparable results were obtained when PCT variation between D-2 and D0, or D-3 and D0 were considered. In contrast, CRP elevation, leukocyte count and fever had a poor predictive value in our population.. PCT monitoring could be helpful in the early diagnosis of nosocomial infection in the ICU. Both absolute values and variations should be considered and evaluated in further studies.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Cross Infection; Early Diagnosis; Female; Hospitals, Teaching; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve

Every day, critical care physicians around the world face the same challenge of the optimal timing of antimicrobial administration: when to start and when to stop antibiotics. Duration of antibiotic therapy for sepsis is mostly based on expert opinion, but its reduction is arguably the most promising approach to decrease emergence and selection of antibiotic resistance. The study by Hochreiter and colleagues presents another piece of evidence suggesting that procalcitonin may indeed be a valuable diagnostic parameter to guide antibiotic treatment duration, despite the ongoing controversy about the diagnostic accuracy of pro-calcitonin.

Topics: Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Decision Making; Drug Administration Schedule; Evidence-Based Medicine; Humans; Protein Precursors; Sepsis; Time Factors

To compare the diagnostic accuracy of neutrophil and monocyte CD64 indexes (CD64in and CD64im) for sepsis in critically ill neonates and children with that of lipopolysaccharide-binding protein (LBP), procalcitonin (PCT) and C-reactive protein (CRP).. Prospective, observational study in a level III multidisciplinary neonatal and pediatric intensive care unit (ICU).. Forty-six neonates and 36 children with systemic inflammatory response syndrome (SIRS) and suspected infection, classified into two groups: those with bacterial sepsis (microbiologically proven or clinical sepsis) and those without bacterial sepsis (infection not supported by subsequent clinical course, laboratory data and microbiological tests).. Flow cytometric CD64in and CD64im, serum LBP, PCT and CRP measurement on 2 consecutive days from admission to the ICU.. There were 17 cases of bacterial sepsis in neonates and 24 cases of bacterial sepsis in children. All neonates and the majority of children were mechanically ventilated, and more than two-thirds of neonates with sepsis and one-third of children with sepsis needed inotropic/vasopressor drugs. The highest diagnostic accuracy for sepsis on the 1st day of suspected sepsis was achieved by LBP in neonates (0.86) and by CD64in in children (0.88) and 24 h later by CD64in in neonates (0.96) and children (0.98).. Neutrophil CD64 index (CD64in) is the best individual marker for bacterial sepsis in children, while in neonates the highest diagnostic accuracy at the time of suspected sepsis was achieved by LBP and 24 h later by CD64in.

Topics: Acute-Phase Proteins; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Child; Child, Preschool; Critical Illness; Female; Flow Cytometry; Humans; Infant; Infant, Newborn; Male; Membrane Glycoproteins; Monocytes; Neutrophils; Prospective Studies; Protein Precursors; Receptors, IgG; ROC Curve; Severity of Illness Index; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome

Invasive candidiasis (IC) outcomes in intensive care units (ICUs) could be improved by the early administration of antifungals. The Candida Score (CS) prediction rule has been proposed for the selection of patients who could develop IC. Procalcitonin (PCT) levels allow prompt identification of sepsis, but their behavior in the setting of IC is unclear. We hypothesize that PCT could be helpful in the early diagnosis of IC in patients with Candida sp. colonization.. Prospective observational study.. Thirty-six ICUs in Spain, Portugal and France.. Every non-neutropenic critically ill patient hospitalized for more than 7 days without concurrent bacterial infection. The CS was calculated weekly. Serums were collected concomitantly.. Two hundred twenty PCT levels were measured in 136 patients [neither colonized nor infected (NCNI): n = 73; multifocal colonization (MF): n = 43; MF + IC: n = 20]. Baseline PCT levels were significantly higher in the MF + IC group than in other groups (p = 0.001). In patients with MF, the highest CS value calculated during the patient's stay was the sole independent predictor of IC. The receiver-operating curve analysis showed that the diagnosis values of PCT and CS were comparable (AUROCC = 0.713, and 0.727, respectively). Moreover, PCT increased the positive predictive value of CS from 44.7 to 59.3%.. After 7 days of hospitalization, PCT levels in patients with MF who go on to develop IC are higher than in others. Serum PCT could also improve the predictive value of CS. PCT together with CS could therefore be considered for the assessment of IC risk.

Topics: Adolescent; Adult; Calcitonin; Calcitonin Gene-Related Peptide; Candidiasis; Critical Illness; Diagnosis, Differential; Female; France; Humans; Male; Middle Aged; Portugal; Prospective Studies; Protein Precursors; Severity of Illness Index; Spain; Young Adult

Procalcitonin (PCT) has been proposed as a diagnostic and prognostic sepsis marker, but has never been validated in febrile patients with prolonged ICU stay.. Patients were included in the study provided they were hospitalised in the ICU for > 10 days, were free of infection and presented a new episode of SIRS, with fever >38 degrees C being obligatory. Fifty patients fulfilled the above criteria. PCT was measured daily during the ICU stay. The primary outcome was proven infection.. Twenty-seven out of 50 patients were diagnosed with infection. Median PCT on the day of fever was 1.18 and 0.17 ng/ml for patients with and without proven infections (p < 0.001). The area under the curve for PCT was 0.85 (95% CI; 0.71-0.93), for CRP 0.65 (0.46-0.78) and for WBC 0.68 (0.49-0.81). A PCT level of 1 ng/mL yielded a negative predictive value of 72% for the presence of infection, while a PCT of 1.16 had a specificity of 100%. A two-fold increase of PCT between fever onset and the previous day was associated with proven infection (p 0.001) (OR = 8.55; 2.4-31.1), whereas a four-fold increase of PCT of any of the 6 preceding days was associated with a positive predictive value exceeding 69.65%. A PCT value less than 0.5 ng/ml on the third day after the advent of fever was associated with favorable survival (p 0.01).. The reported data support that serial serum PCT may be a valuable diagnostic and prognostic marker in febrile chronic critically ill patients.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fever; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Systemic Inflammatory Response Syndrome

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

Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.. review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1st September, 2006 and 31st July, 2007.. 179 episodes of either primary (n = 117) or secondary (n = 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; p < 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16-0.70; p = 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (n = 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699-0.879, vs. 0.934, 95% CI: 0.881-0.970, respectively; p < 0.050).. In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Early Diagnosis; Female; Humans; Leukocyte Count; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sepsis

Topics: Anticoagulants; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Protein Precursors

To assess the diagnostic utility of combining measurement of blood procalcitonin (PCT) concentrations with the presence of a biphasic transmittance waveform (BPW) from the activated partial thromboplastin time (aPTT) to identify sepsis in critically ill patients.. Prospective observational study.. Thirty-one-bed university hospital department of medico-surgical intensive care.. Two hundred consecutive adult patients admitted to the department during a 3-month period.. aPTT waveform analysis was performed on admission and daily throughout the intensive care unit (ICU) stay. Receiver operating characteristic curves were created to determine the best threshold values of BPW and PCT for prediction of sepsis. Of the 200 patients, 63 (32%) had sepsis during the ICU stay; 29 (15%) patients were diagnosed with sepsis at admission. Using a threshold value of BPW slope_1 = -0.075%T/sec, 37 patients (19%) had a BPW at ICU admission and 84 (42%) at some time during the ICU stay. At this threshold, 23 of the patients (62%) with a BPW at admission and 51 (61%) with a BPW during the ICU stay were diagnosed with sepsis. Using a cut-off value of 1 ng/ml, 60 patients (30%) had abnormal PCT at admission, and 86 during the ICU stay. At this threshold, 24 of the patients (40%) with abnormal PCT at admission and 52 (60%) with abnormal PCT during the ICU stay were diagnosed with sepsis. Thirty patients had a BPW and an abnormal PCT, and 23 (77%) of these had sepsis. Of the other 170 patients, only six patients (4%) had sepsis. Hence, the sensitivity of the combination of BPW and PCT at admission was 79% and specificity 96%; the negative predictive value was 96%.. aPTT waveform analysis is an easy and rapid method for identification of sepsis; its combination with PCT increases its specificity.

Topics: Acute Disease; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Protein Precursors; Sepsis

You are concerned about the escalating use of antibiotics in your intensive care unit (ICU). This has put a strain on the ICU budget and is possibly resulting in the emergence of resistant bacteria. You review the situation with your team and one suggestion is to consider using biomarkers such as procalcitonin to better guide appropriate antibiotic decision making.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Trials as Topic; Critical Care; Critical Illness; Decision Making; Humans; Protein Precursors

To compare the accuracy of procalcitonin and C-reactive protein as diagnostic markers of bacterial infection in critically ill children at the onset of systemic inflammatory response syndrome (SIRS).. Prospective cohort study.. Tertiary care, university-affiliated pediatric intensive care unit (PICU).. Consecutive patients with SIRS.. From June to December 2002, all PICU patients were screened daily to include cases of SIRS. At inclusion (onset of SIRS), procalcitonin and C-reactive protein levels as well as an array of cultures were obtained. Diagnosis of bacterial infection was made a posteriori by an adjudicating process (consensus of experts unaware of the results of procalcitonin and C-reactive protein). Baseline and daily data on severity of illness, organ dysfunction, and outcome were collected.. Sixty-four patients were included in the study and were a posteriori divided into the following groups: bacterial SIRS (n = 25) and nonbacterial SIRS (n = 39). Procalcitonin levels were significantly higher in patients with bacterial infection compared with patients without bacterial infection (p = .01). The area under the receiver operating characteristic curve for procalcitonin was greater than that for C-reactive protein (0.71 vs. 0.65, respectively). A positive procalcitonin level (>or=2.5 ng/mL), when added to bedside clinical judgment, increased the likelihood of bacterial infection from 39% to 92%, while a negative C-reactive protein level (<40 mg/L) decreased the probability of bacterial infection from 39% to 2%.. Procalcitonin is better than C-reactive protein for differentiating bacterial from nonbacterial SIRS in critically ill children, although the accuracy of both tests is moderate. Diagnostic accuracy could be enhanced by combining these tests with bedside clinical judgment.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Critical Illness; Female; Hospitals, University; Humans; Intensive Care Units, Pediatric; Male; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Systemic Inflammatory Response Syndrome

To estimate the diagnostic value of serum PCT, CRP, leukocyte count and temperature as markers of sepsis in critically ill ICU burn patients.. Prospective, observational study in a four bed Burn Intensive Care Unit.. Forty-three patients admitted in a Burn ICU were included in our study.. Serum PCT, CRP concentrations, WCC (white cell count), neutrophils and temperature were measured within the first 24h after-burn and daily thereafter. Severity of organ failure was estimated by sequential organ failure assessment (SOFA) score. Every day we classified all patients in one of the following three categories: non-systemic inflammatory condition (non-SIRS), SIRS non-infected and SIRS 2 infected or sepsis. Patients with infected SIRS differ significantly from non-infected SIRS in PCT (11.8+/-15.8 versus 0.63+/-0.0.43, respectively, p < 0.001). On the other hand, WCC, temperature and neutrophils did not differ significantly between patients with SIRS non-infected and infected SIRS. CRP was elevated in all three groups but didn't differ significantly between SIRS non-infected and septic patients. Area under receiver operating curves was 0.975 and showed reasonable discriminative power (p = 0.002, 95% CI, 0.91-1.035) in predicting of sepsis only for PCT.. Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injury.

Topics: Analysis of Variance; Biomarkers; Body Temperature; Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Humans; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Markers of inflammation, such as C-reactive protein (CRP) and white blood cell count, have, because of their low specificity, proven far from ideal in identifying patients with sepsis. Procalcitonin (PCT) has been shown to be a useful marker for differentiating patients with bacterial infection from other acute inflammatory conditions. Corticosteroid therapy has been demonstrated to be effective for treating patients with septic shock, late-phase acute respiratory distress syndrome (ARDS), or functional adrenal insufficiency, and the use of corticosteroid in critical illness has recently increased. It is also well established that corticosteroid modulate inflammatory variables in acute inflammatory conditions. The purpose of this study was to evaluate the clinical usefulness of PCT measurement for assessing the severity of bacterial infection in patients requiring corticosteroid therapy.. Six patients with confirmed bacterial infectious diseases or suspected infectious diseases and requiring corticosteroid therapy were enrolled in the study. Levels of PCT and CRP were measured. The Sequential Organ Failure Assessment (SOFA) score and the Acute Physiology and Chronic Health Evaluation (APACHE) II score were calculated to evaluate the severity of sepsis.. 1) There was no significant correlation between the serum concentration of PCT and the plasma level of CRP in patients requiring corticosteroid therapy. 2) The PCT concentration was significantly correlated with the SOFA score (R(2)=0.467, p<0.0001) and the APACHE II score (R(2)=0.308, p=0.0003). However, no significant correlations was found between the CRP concentration and the SOFA score (R(2)=0.054, p=0.15) or the APACHE II score (R(2)=0.043, p=0.20). 3) Data sets were divided into two groups: septic shock and non-septic shock. No significant differences were present in CRP levels between the groups. However, significant differences were apparent in PCT concentrations (p<0.001).. PCT can be a more sensitive and useful marker than CRP for evaluating the severity and progression of sepsis in patients requiring corticosteroid therapy. Further studies are needed to confirm these results in larger groups of patients.

Topics: Adrenal Cortex Hormones; Aged; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Protein Precursors; Severity of Illness Index

Identification of postoperative patients at high risk of dying early after intensive care unit (ICU) admission through a fast and readily available parameter may help in determining therapeutic interventions or further diagnostic procedures that could have an impact on patients' outcome. The aim of our study was to assess the utility of procalcitonin (PCT) and other readily available parameters, as useful early (days 1-3) predictors of mortality in postoperative patients diagnosed with severe sepsis within 24 h preceding their operation.. More than a period of 2 yr, subsets of 69 postoperative patients admitted with severe sepsis and 890 non-septic ICU patients were investigated. PCT, C-reactive protein (CRP) and sequential organ failure assessment (SOFA) score were recorded over the duration of ICU stay.. PCT area under receiver operating characteristic (ROC) curve was 0.78 on day 3 and was highly predictive of fatal outcome (0.90) at day 6. Area under ROC curve of SOFA score was 0.85 on day 3 and remained in this range until day 6. Area under ROC curves on day 3 of CRP (0.61) was non-predictive and remained non-predictive over the duration of ICU stay.. PCT exhibited no discriminative power early after ICU admission for prediction of mortality in critically ill patients with severe sepsis, compared with a high predictive power of SOFA score on day 3. However, using PCT could still serve as a useful complementary comparator for prediction of survival outcome using the SOFA score.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Humans; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Prognosis; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Survival Analysis

Candidemia is a life-threatening infection in the ICU whose prognosis is highly dependent on the stage at which it is recognized. Procalcitonin (PCT) levels have been shown to accurately distinguish between bacteremia and noninfectious inflammatory states in critically ill patients with clinical signs of sepsis. Little is known about the accuracy of PCT for the diagnosis of candidemia in this setting.. A medical intensive care unit in a teaching hospital.. Review of the medical records of every non-neutropenic patient with either bacteremia or candidemia and clinical sepsis in whom PCT dosage at the onset of infection was available between May 2004 and December 2005.. Fifty episodes of either bacteremia (n=35) or candidemia (n=15) were included. PCT levels were found to be markedly higher in patients with bacteremia than in those with candidemia. Moreover, a low PCT value was found to be an independent predictor of candidemia in the study population. According to the calculation of the area under the receiver operating characteristic curve, PCT was found to be accurate in distinguishing between candidemia and bacteremia (0.96 [0.03]). A PCT level of higher than 5.5 ng/ml yields a 100% negative predictive value and a 65.2% positive predictive value for candidemia-related sepsis.. A high PCT value in a critically ill non-neutropenic patient with clinical sepsis is unlikely in the setting of candidemia.

Topics: Aged; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Candidiasis; Chi-Square Distribution; Critical Illness; Diagnosis, Differential; Early Diagnosis; Female; Humans; Leukocyte Count; Logistic Models; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; ROC Curve

To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients.. Prospective observational cohort study.. : Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital, a tertiary reference hospital in Denmark.. Four hundred seventy-two patients with diverse comorbidity and age admitted to this intensive care unit.. Equal in all patient groups: antimicrobial treatment adjusted according to the procalcitonin level.. Daily procalcitonin measurements were carried out during the study period as well as measurements of white blood cell count and C-reactive protein and registration of comorbidity. The primary end point was all-cause mortality in a 90-day follow-up period. Secondary end points were mortality during the stay in the intensive care unit and in a 30-day follow-up period. A total of 3,642 procalcitonin measurements were evaluated in 472 critically ill patients. We found that a high maximum procalcitonin level and a procalcitonin increase for 1 day were independent predictors of 90-day all-cause mortality in the multivariate Cox regression analysis model. C-reactive protein and leukocyte increases did not show these qualities. The adjusted hazard ratio for procalcitonin increase for 1 day was 1.8 (95% confidence interval 1.3-2.7). The relative risk for mortality in the intensive care unit for patients with an increasing procalcitonin was as follows: after 1 day increase, 1.8 (95% confidence interval 1.4-2.4); after 2 days increase, 2.2 (95% confidence interval 1.6-3.0); and after 3 days increase: 2.8 (95% confidence interval 2.0-3.8).. A high maximum procalcitonin level and a procalcitonin increase for 1 day are early independent predictors of all-cause mortality in a 90-day follow-up period after intensive care unit admission. Mortality risk increases for every day that procalcitonin increases. Levels or increases of C-reactive protein and white blood cell count do not seem to predict mortality.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Denmark; Female; Humans; Infant; Leukocyte Count; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Survival Analysis

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Denmark; Humans; Multiple Organ Failure; Prognosis; Protein Precursors; Sepsis

To evaluate markers of infection in critically ill neonates and children, comparing lipopolysaccharide-binding protein (LBP) with procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP).. Prospective, observational study in the level III multidisciplinary neonatal and pediatric intensive care unit.. Sixty patients with systemic inflammatory response syndrome (SIRS) and suspected infection classified into two groups: SIRS/sepsis ( n=33) and SIRS/no sepsis ( n=27). We included 29 neonates aged less than 48 h (neonates <48 h), 12 neonates older than 48 h (neonates >48 h), and 19 children. Median disease severity was high in neonates aged under 48 h and moderate in neonates aged over 48 h and children.. Serum LBP, PCT, IL-6, and CRP were measured on two consecutive days. Area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and predictive values were evaluated.. Serum LBP was higher in patients with SIRS/sepsis than in patients with SIRS/no sepsis. AUC for LBP on the first day of suspected infection was 0.89 in the younger neonates, 0.93 in the older neonates, and 0.91 in children.. In critically ill neonates aged under 48 h LBP on the first day of suspected infection is a better marker of sepsis than IL-6 and PCT, and is similar to CRP. In critically ill neonates aged over 48 h and children LBP is a better marker than IL-6 and CRP, and is similar to PCT.

Topics: Acute-Phase Proteins; Adolescent; Age Factors; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Child; Child, Preschool; Critical Illness; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care Units, Pediatric; Interleukin-6; Membrane Glycoproteins; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Critical Care; Critical Illness; Humans; Prognosis; Protein Precursors

It is still unclear as to whether the paradoxical arteriovenous carboxyhemoglobin (COHb) difference found in critical illness may represent a novel marker of the acute inflammatory response. We determined whether the arterial and central venous COHb concentration or their difference may be correlated to classical pro-inflammatory markers.. Arterial and matched central venous blood gases were obtained from non-smoking intensive care patients undergoing gastrointestinal surgery, and were correlated with plasma concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and leukocytes.. No correlation was found between arteriovenous COHb difference and the investigated pro-inflammatory mediators. While arterial and central venous COHb concentrations were positively correlated to plasma concentrations of TNF-alpha (P< or =0.01), IL-6 (P<0.05) and PCT (P< or =0.01), they were neither interrelated with PCT nor with leukocytes.. Arteriovenous COHb difference does not appear to be a marker of the acute inflammatory response. Future studies are needed to investigate whether arterial and central venous COHb concentrations by themselves may serve as indicators of systemic inflammation.

Topics: Blood Gas Analysis; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carboxyhemoglobin; Critical Illness; Female; Humans; Inflammation Mediators; Interleukin-6; Leukocytes; Male; Middle Aged; Protein Precursors; Tumor Necrosis Factor-alpha

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Infections; Neopterin; Protein Precursors

Procalcitonin (PCT) is a potentially useful marker in pediatric Emergency Departments (ED). The basic objectives of this study were to assess the diagnostic performance of PCT for distinguishing between viral and bacterial infections and for the early detection of invasive bacterial infections in febrile children between 1 and 36 months old comparing it with C-reactive protein (CRP) and to evaluate the utility of a qualitative rapid test for PCT in ED.. Prospective, observational and multicenter study that included 445 children who were treated for fever in pediatric ED. Quantitative and qualitative plasma values of PCT and CRP were correlated with the final diagnosis. To obtain the qualitative level of PCT the BRAHMS PCT-Q rapid test was used.. Mean PCT and CRP values in viral infections were 0.26 ng/ml and 15.5 mg/l, respectively. The area under the curve obtained for PCT in distinguishing between viral and bacterial infections was 0.82 (sensitivity, 65.5%; specificity, 94.3%; optimum cutoff, 0.53 ng/ml), whereas for CRP it was 0.78 (sensitivity, 63.5%; specificity, 84.2%; optimum cutoff, 27.5 mg/l). PCT and CRP values in invasive infections (PCT, 24.3 ng/ml; CRP 96.5 mg/l) were significantly higher than those for noninvasive infections (PCT, 0.32 ng/ml; CRP, 23.4 mg/l). The area under the curve for PCT was 0.95 (sensitivity, 91.3%; specificity, 93.5%; optimum cutoff, 0.59 ng/ml), significantly higher (P < 0.001) than that obtained for CRP (0.81). The optimum cutoff value for CRP was >27.5 mg/l with sensitivity and specificity of 78 and 75%, respectively. In infants in whom the evolution of fever was <12 h (n = 104), the diagnostic performance of PCT was also greater than that of CRP (area under the curve, 0.93 for PCT and 0.69 for CRP; P < 0.001). A good correlation between the quantitative values for PCT and the PCT-Q test was obtained in 87% of cases (kappa index, 0.8). The sensitivity of the PCT-Q test (cutoff >0.5 ng/ml) for detecting invasive infections and differentiating them from noninvasive infections was 90.6%, with a specificity of 83.6%.. PCT offers better specificity than CRP for differentiating between the viral and bacterial etiology of the fever with similar sensitivity. PCT offers better sensibility and specificity than CRP to differentiate between invasive and noninvasive infection. PCT is confirmed as an excellent marker in detecting invasive infections in ED and can even make early detection possible of invasive infections if the evolution of the fever is <12 h. The PCT-Q test has a good correlation with the quantitative values of the marker.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Critical Illness; Diagnosis, Differential; Emergency Service, Hospital; Female; Fever of Unknown Origin; Hospitals, Pediatric; Humans; Infant; Infant, Newborn; Male; Predictive Value of Tests; Probability; Protein Precursors; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Viremia

To evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein, leukocyte count, D-dimer, and antithrombin III at onset of septic episode and 24 h later in prediction of hospital mortality in critically ill patients with suspected sepsis.. Prospective, cohort study in two university hospital intensive care units.. 61 critically ill patients with suspected sepsis.. The outcome measure was hospital mortality. Hospital survivors ( n=41) and nonsurvivors ( n=20) differed statistically significantly on day 1 (admission) in PCT, IL-6, SOFA score, and APACHE II score, and 24 h later in PCT, IL-6, and D-dimer values. AT III, CRP, and leukocyte count did not differ. The areas under receiver operating curves showed reasonable discriminative power (>0.75) in predicting hospital mortality only for day 2 IL-6 (0.799) and day 2 PCT (0.777) values which were comparable to that of APACHE II (0.786), and which remained the only independent predictor of mortality.. Admission and day 2 IL-6, and day 2 PCT, and day 2 D-dimer values differed significantly between hospital survivors and nonsurvivors among critically ill patients with suspected sepsis. However, in prediction of hospital mortality, only the discriminative power of day 2 PCT and IL-6 values, and APACHE II was reasonable as judged by AUC analysis (>0.75).

Topics: Adult; Antithrombin III; APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fibrin Fibrinogen Degradation Products; Finland; Hospital Mortality; Humans; Interleukin-6; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prognosis; Protein Precursors; Sepsis

To define the role of procalcitonin in the differential diagnosis, prognosis and follow-up of critically ill patients.. Prospective study during the 2-year period from January 1998-2000.. One hundred nineteen critically ill patients: 29 with systemic inflammatory response syndrome (SIRS) without any signs of infection, 11 with sepsis, 17 with severe sepsis, 10 with septic shock and 52 controls. Daily measurements of procalcitonin were performed by an immunocheminoluminometric assay, and values were correlated to the clinical characteristics of the patients.. Mean concentrations of procalcitonin were 5.45 (95% CI: 2.11, 8.81), 7.29 (95% CI: -1.92,14.59), 6.26 (95% CI: -1.32, 13.85) and 38.76 ng/ml (95% CI: 0.15, 77.38) on the 1st day in patients with SIRS, sepsis, severe sepsis and septic shock, respectively, and were statistically superior to those of control patients. Procalcitonin was gradually diminished over time with the resolution of the syndrome, while it was sustained in the same or more augmented levels upon worsening. Mean concentrations of procalcitonin on the 1st day for patients finally progressing to ARDS, to ARDS and acute renal failure, to ARDS, acute renal failure and DIC and to ARDS, acute renal failure, DIC and hepatic failure were 10.48, 8.08, 32.72 and 43.35 ng/ml, respectively. ROC curves of the sensitivity and specificity of procalcitonin for the evaluation of SIRS and sepsis were similar.. The definite differential diagnosis between SIRS and sepsis may not rely on a single application of procalcitonin but on the complete clinical and laboratory evaluation of the patient with procalcitonin playing a considerable role. Procalcitonin is an early prognostic marker of the advent of MODS; therefore, daily determinations might help in the follow-up of the critically ill patient.

Topics: Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Diagnosis, Differential; Female; Greece; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Systemic Inflammatory Response Syndrome

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 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

Procalcitonin (PCT) plasma concentrations and its kinetic can be used as a diagnostic tool in critically ill patients and patients with sepsis. Since renal dysfunction is a frequent complication in these patients, and PCT is a protein with a low molecular weight, we have measured the half-life time of PCT after peak concentrations in patients with normal and impaired renal function. We also have analyzed the influence of patients age and gender on PCT elimination kinetics.. Prospective clinical study. Renal dysfunction was assessed by plasma creatinine. The half-life time of PCT was evaluated 24 and 48 h after acute induction of PCT, when the focus of PCT induction has rapidly been eliminated.. Intensive care unit of our University hospital, a tertiary health care institution.. 69 patients were included into the study.. None.. The half-life-time of PCT was not significantly altered during renal dysfunction (26.1-33.1 h, 25-50 percentiles, creatinine clearance < 30 ml/min) when compared with normal renal function (22.3-28.9 h). It neither correlated with creatinine clearance (p=0.14), nor age (p=0.99) or gender (p=0.90, Pearson product-moment correlation).. The data of the present study demonstrate that assessment of PCT kinetic can also be used for diagnostic and prognostic reasons in patients with renal dysfunction. It may, however, exceed 24 h also in patients with normal renal function. As to the present knowledge, renal secretion does not contribute as a main pathway to PCT elimination.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Germany; Half-Life; Humans; Intensive Care Units; Kidney Function Tests; Prospective Studies; Protein Precursors; Renal Insufficiency; Sepsis; Severity of Illness Index; Statistics, Nonparametric

Topics: Albuminuria; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Critical Care; Critical Illness; Esophagectomy; Follow-Up Studies; Glycoproteins; Humans; Protein Precursors; Sensitivity and Specificity; Sepsis; Time Factors

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

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

Monitoring the immune responses in critically ill patients helps us to understand pathophysiological aspects of inflammation, immune deficiency, and infection, and to assess objective measures of therapeutic success. Monitoring should be adapted to the individual therapeutic approach. We recommend the measurement of substances in plasma that indicate systemic inflammatory processes, such as tumour necrosis factor (TNF), interleukin (IL)-6, and C-reactive protein (CRP), and invasive infection or endotoxaemia, such as procalcitonin (PCT). Moreover, it is important to evaluate the functional activity of the immune system, which can fail like other organs in the process of multiple organ failure. The resulting immunodeficiency results in failure to eliminate invading pathogens. Plasma concentration of IL-10 and of monocytic function and phenotype (HLA-DR+, CD14+ monocytes, ex vivo TNF secretion capacity) are the most valuable measurements for this purpose.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Critical Illness; Endotoxemia; Glycoproteins; HLA-DR Antigens; Humans; Immunoglobulin A; Immunoglobulin M; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Interleukin-10; Interleukin-6; Lipopolysaccharide Receptors; Mediastinitis; Monitoring, Immunologic; Monocytes; Multiple Organ Failure; Protein Precursors; Surgical Wound Infection; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha