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      Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study

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          Abstract

          Introduction

          Measurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores.

          Method

          We evaluated blood samples from 101 consecutive critically ill patients admitted to the intensive care unit and from 160 age-matched healthy control individuals. The patients had initially been enrolled in a prospective observational study investigating the prognostic value of endocrine dysfunction in critically ill patients ("PEDCRIP" Study). The prognostic value of MR-proADM levels was compared with those of two physiological scores and of various biomarkers (for example C-reactive Protein, IL-6, procalcitonin). MR-proADM was measured in EDTA plasma from all patients using a new sandwich immunoassay.

          Results

          On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 48 had systemic inflammatory response syndrome. Median MR-proADM levels on admission (nmol/l [range]) were 1.1 (0.3–3.7) in patients with systemic inflammatory response syndrome, 1.8 (0.4–5.8) in those with sepsis, 2.3 (1.0–17.6) in those with severe sepsis and 4.5 (0.9–21) in patients with septic shock. In healthy control individuals the median MR-proADM was 0.4 (0.21–0.97). On admission, circulating MR-proADM levels in patients with sepsis, severe sepsis, or septic shock were significantly higher in nonsurvivors (8.5 [0.8–21.0]; P < 0.001) than in survivors (1.7 [0.4–17.6]). In a receiver operating curve analysis of survival of patients with sepsis, the area under the curve (AUC) for MR-proADM was 0.81, which was similar to the AUCs for IL-6, Acute Physiology and Chronic Health Evaluation II score and Simplified Acute Physiology Score II. The prognostic value of MR-proADM was independent of the sepsis classification system used.

          Conclusion

          MR-proADM may be helpful in individual risk assessment in septic patients.

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          Most cited references29

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          American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.

          (1992)
          To define the terms "sepsis" and "organ failure" in a precise manner. Review of the medical literature and the use of expert testimony at a consensus conference. American College of Chest Physicians (ACCP) headquarters in Northbrook, IL. Leadership members of ACCP/Society of Critical Care Medicine (SCCM). An ACCP/SCCM Consensus Conference was held in August of 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic variables by which a patient could be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods were recommended when dealing with septic patients as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae.
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            APACHE-acute physiology and chronic health evaluation: a physiologically based classification system.

            Investigations describing the utilization pattern and documenting the value of intensive care are limited by the lack of a reliable and valid classification system. In this paper, the authors describe the development and initial validation of acute physiology and chronic health evaluation (APACHE), a physiologically based classification system for measuring severity of illness in groups of critically ill patients. APACHE uses information available in the medical record. In studies on 582 admissions to a university hospital ICU and 223 admissions to a community hospital ICU, APACHE was reliable in classifying ICU admissions. In validation studies involving these 805 admissions, the acute physiology score of APACHE demonstrated consistent agreement with subsequent therapeutic effort and mortality. This was true for a broad range of patient groups using a variety of sensitivity analyses. After successful completion of multi-institutional validation studies, the APACHE classification system could be used to control for case mix, compare outcomes, evaluate new therapies, and study the utilization of ICUs.
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              Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit.

              The diagnosis of infection in critically ill patients is challenging because traditional markers of infection are often misleading. For example, serum concentrations of calcitonin precursors are increased in patients with infections. However, their predictive accuracy for the diagnosis of sepsis in unselected patients in a medical intensive care unit (ICU) is unknown. Therefore, we compared the usefulness of serum concentrations of calcitonin precursors, C-reactive protein, interleukin-6, and lactate for the diagnosis of sepsis in consecutive patients suffering from a broad range of diseases with an anticipated stay of > or =24 hrs in a medical ICU. Prospective cohort study. Medical intensive care unit in a university medical center. 101 consecutive critically ill patients. None. Blood samples were collected at various time points during the course of the disease. Systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock were diagnosed according to standardized criteria, and patients were reclassified daily without prior knowledge of the serum concentrations of calcitonin precursors or interleukin-6. At admission, 99% of the patients had systemic inflammatory response syndrome, 53% had sepsis, and 5% developed sepsis during their stay in the ICU. Calcitonin precursors, C-reactive protein, interleukin-6, and lactate levels increased with the severity of infection (p 1 ng/mL had sensitivity of 89% and specificity of 94% for the diagnosis of sepsis. High serum concentrations of calcitonin precursors were associated with poor prognosis (p = .01). In a medical ICU, serum calcitonin precursor concentrations are more sensitive and are specific markers of sepsis as compared with serum C-reactive protein, interleukin-6, and lactate levels.
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                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                2005
                15 November 2005
                : 9
                : 6
                : R816-R824
                Affiliations
                [1 ]Department of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
                [2 ]Research Department, Brahms AG, Hennigsdorf/Berlin, Neuendorfstrasse 25, 16761 Hennigsdorf, Germany
                [3 ]Research Department, Brahms AG, Hennigsdorf/Berlin, Neuendorfstrasse 25, 16761 Hennigsdorf, Germany
                [4 ]Division of Hospital Epidemiology, University Hospital Geneva, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland
                [5 ]Research Department, Brahms AG, Hennigsdorf/Berlin, Neuendorfstrasse 25, 16761 Hennigsdorf, Germany
                [6 ]Department of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
                Article
                cc3885
                10.1186/cc3885
                1414007
                16356231
                e72b5004-2c31-4b66-aab0-29ead89dfc4a
                Copyright © 2005 Christ-Crain 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
                : 10 May 2005
                : 13 June 2005
                : 22 September 2005
                : 29 September 2005
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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