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      Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis

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          Abstract

          Background

          The immature granulocyte count has been reported to be a marker of infection and sepsis. The difference in leukocyte subfractions (delta neutrophil index, DNI) in ADVIA 2120 reflects the fraction of circulating immature granulocytes in the blood. This study evaluated the clinical utility of DNI as a severity and prediction marker in critically ill patients with sepsis.

          Methods

          One hundred and three patients admitted to the medical intensive care unit with sepsis were studied. DNI (the difference in leukocyte subfractions identified by myeloperoxidase and nuclear lobularity channels) was determined using a specific blood cell analyzer.

          Results

          Forty four patients (42.7%) were diagnosed with severe sepsis/septic shock. Overt disseminated intravascular coagulation (DIC) occurred in 40 (38.8%). DNI was significantly higher in patients with severe sepsis/septic shock and overt DIC than in patients without ( p < 0.05). DNI correlated with DIC score (r = 0.54, p < 0.001). We observed a monotonic increase in the proportion of overt DIC and severe sepsis/septic shock associated with increasing quartiles of DNI ( p < 0.001). A DNI value > 6.5% was a better indicator of severe sepsis/septic shock than C-reactive protein, lactate, white blood cell count, and absolute neutrophil count (sensitivity, 81.3%; specificity, 91.0%; positive predictive value, 88.6%; and negative predictive value, 84.7%). In 36 (82%) of the 44 patients with severe sepsis/septic shock, DNI values were already elevated up to 12 hours before the onset of organ/circulatory failure.

          Conclusions

          DNI may be used as a marker of disease severity in critically ill patients with sepsis. High levels of DNI may help to identify patients with an impending risk of developing severe sepsis/septic shock.

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          Most cited references20

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          SAPS 3—From evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission

          Objective To develop a model to assess severity of illness and predict vital status at hospital discharge based on ICU admission data. Design Prospective multicentre, multinational cohort study. Patients and setting A total of 16,784 patients consecutively admitted to 303 intensive care units from 14 October to 15 December 2002. Measurements and results ICU admission data (recorded within ±1 h) were used, describing: prior chronic conditions and diseases; circumstances related to and physiologic derangement at ICU admission. Selection of variables for inclusion into the model used different complementary strategies. For cross-validation, the model-building procedure was run five times, using randomly selected four fifths of the sample as a development- and the remaining fifth as validation-set. Logistic regression methods were then used to reduce complexity of the model. Final estimates of regression coefficients were determined by use of multilevel logistic regression. Variables selection and weighting were further checked by bootstraping (at patient level and at ICU level). Twenty variables were selected for the final model, which exhibited good discrimination (aROC curve 0.848), without major differences across patient typologies. Calibration was also satisfactory (Hosmer-Lemeshow goodness-of-fit test Ĥ=10.56, p=0.39, Ĉ=14.29, p=0.16). Customised equations for major areas of the world were computed and demonstrate a good overall goodness-of-fit. Conclusions The SAPS 3 admission score is able to predict vital status at hospital discharge with use of data recorded at ICU admission. Furthermore, SAPS 3 conceptually dissociates evaluation of the individual patient from evaluation of the ICU and thus allows them to be assessed at their respective reference levels. Electronic Supplementary Material Electronic supplementary material is included in the online fulltext version of this article and accessible for authorised users: http://dx.doi.org/10.1007/s00134-005-2763-5
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            Septic shock.

            Septic shock, the most severe complication of sepsis, is a deadly disease. In recent years, exciting advances have been made in the understanding of its pathophysiology and treatment. Pathogens, via their microbial-associated molecular patterns, trigger sequential intracellular events in immune cells, epithelium, endothelium, and the neuroendocrine system. Proinflammatory mediators that contribute to eradication of invading microorganisms are produced, and anti-inflammatory mediators control this response. The inflammatory response leads to damage to host tissue, and the anti-inflammatory response causes leucocyte reprogramming and changes in immune status. The time-window for interventions is short, and treatment must promptly control the source of infection and restore haemodynamic homoeostasis. Further research is needed to establish which fluids and vasopressors are best. Some patients with septic shock might benefit from drugs such as corticosteroids or activated protein C. Other therapeutic strategies are under investigation, including those that target late proinflammatory mediators, endothelium, or the neuroendocrine system.
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              SAPS 3—From evaluation of the patient to evaluation of the intensive care unit. Part 1: Objectives, methods and cohort description

              Objective Risk adjustment systems now in use were developed more than a decade ago and lack prognostic performance. Objective of the SAPS 3 study was to collect data about risk factors and outcomes in a heterogeneous cohort of intensive care unit (ICU) patients, in order to develop a new, improved model for risk adjustment. Design Prospective multicentre, multinational cohort study. Patients and setting A total of 19,577 patients consecutively admitted to 307 ICUs from 14 October to 15 December 2002. Measurements and results Data were collected at ICU admission, on days 1, 2 and 3, and the last day of the ICU stay. Data included sociodemographics, chronic conditions, diagnostic information, physiological derangement at ICU admission, number and severity of organ dysfunctions, length of ICU and hospital stay, and vital status at ICU and hospital discharge. Data reliability was tested with use of kappa statistics and intraclass-correlation coefficients, which were >0.85 for the majority of variables. Completeness of the data was also satisfactory, with 1 [0–3] SAPS II parameter missing per patient. Prognostic performance of the SAPS II was poor, with significant differences between observed and expected mortality rates for the overall cohort and four (of seven) defined regions, and poor calibration for most tested subgroups. Conclusions The SAPS 3 study was able to provide a high-quality multinational database, reflecting heterogeneity of current ICU case-mix and typology. The poor performance of SAPS II in this cohort underscores the need for development of a new risk adjustment system for critically ill patients. Electronic Supplementary Material Electronic supplementary material is included in the online fulltext version of this article and accessible for authorised users: http://dx.doi.org/10.1007/s00134-005-2762-6
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                Author and article information

                Journal
                BMC Infect Dis
                BMC Infectious Diseases
                BioMed Central
                1471-2334
                2011
                1 November 2011
                : 11
                : 299
                Affiliations
                [1 ]Pulmonary and Critical Care Division, Department of Internal Medicine, Severance Hospital, Seoul, Korea
                [2 ]The Institute of Chest Diseases, Yonsei University College of Medicine, Seoul, Korea
                Article
                1471-2334-11-299
                10.1186/1471-2334-11-299
                3213213
                22040292
                ddaac835-6b9d-4f22-b90a-97bf8a673ee6
                Copyright ©2011 Park et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 August 2011
                : 1 November 2011
                Categories
                Research Article

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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