Advances in Clinical Chemistry

1. Auflage 2014
ISBN: 978-0-12-800303-9
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 65, 240 Seiten

Reihe: Advances in Clinical Chemistry

Volume 65 in the internationally acclaimed Advances in Clinical Chemistry contains chapters authored by world renowned clinical laboratory scientists, physicians and research scientists. The serial provides the latest and most up-to-date technologies related to the field of Clinical Chemistry and is the benchmark for novel analytical approaches in the clinical laboratory. - Expertise of international contributors - Latest cutting-edge technologies - Comprehensive in scope

Autoren/Hrsg.

Leseproben

Chapter Two Diagnosis of Infection in Critical Care
Belén Prieto*; Francisco V. Álvarez Menéndez*,†,1    * Clinical Biochemistry, Laboratory of Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
† Biochemistry and Molecular Biology Department, University of Oviedo, Oviedo, Spain
1 Corresponding author: email address: [e-mail] Abstract
Sepsis is the primary cause of death in the intensive care unit. The prevention of sepsis complications requires an early and accurate diagnosis as well as the appropriate monitoring. A deep knowledge of the immunologic basis of sepsis is essential to better understand the scope of incorporating a new marker into clinical practice. Besides revising this theoretical aspect, the current available tools for bacterial identification have been briefly reviewed as well as a variety of new markers showing either well-recognized or potential usefulness for diagnosis and prognosis of infections in critically ill patients. Particular conditions such as community-acquired pneumonia, pediatric sepsis, or liver transplantation, among others, have been separately treated, since the optimal approaches and markers might be different in these special cases. Keywords Biomarkers Infection Sepsis Systemic inflammatory response syndrome Abbreviations AdVs adenoviruses AKI acute kidney injury AUC area under the curve BC blood culture CAP community-acquired pneumonia cfDNA cell-free DNA CI confidence interval CNS central nervous system CRP C-reactive protein CT-proET-1 carboxyterminal fragment of proendotelin-1 DAMPs danger-associated molecular patterns GCS Glasgow Coma Scale HMGB-1 high-mobility group box-1 ICU intensive care unit IL interleukin iNOS inducible nitric oxide synthase MALDI matrix-assisted laser desorption ionization MR-proADM midregional proadrenomedullin MR-proANP medium region of pro A-type natriuretic peptide MS mass spectrometry NF-?B nuclear factor ?B NO nitric oxide NSE neuron-specific enolase OLT orthotopic liver transplantation PAI-1 plasminogen activator inhibitor type 1 PCT procalcitonin PRR pattern-recognition receptors PSI pneumonia severity index PSP/reg pancreatic stone peptide/regenerating peptide SIRS systemic inflammatory response syndrome ST signal transduction TF transcription factor TFPI tissue factor pathway inhibitor TLRs toll-like receptors TNF tumoral necrosis factor TOF time of flight 1 Background
Sepsis is the primary cause of death in the intensive care unit (ICU). Early antibiotic therapy plays a crucial role on the prognosis of these patients. The prevention of sepsis complications requires an early and accurate diagnosis as well as the appropriate monitoring. At present, most microbiological laboratories are limited by poor sensitivity and the time-consuming nature of culture-based methods. The clinical symptoms of the septic patient are often masked by systemic inflammatory response processes, infectious or not, and treatments. The diagnostic difficulty of sepsis is even more relevant in both pediatric and adult ICUs, where patients are at increased risk because of not only their critical state and immunological vulnerability but also the use of invasive techniques (e.g., mechanical ventilation) and nonspecific symptoms. Moreover, the preventive administration of antibiotics in critical care patients increases resistance and the risk of hospital-acquired infections. On the other hand, time factor also plays an important role in the prognosis of sepsis, since a delay in the identification and appropriate management of critical patients during the first 6 h of admission to the ICU is associated with higher mortality [1]. The concept of systemic inflammatory response syndrome (SIRS) was established for the first time at the Sepsis Consensus Conference held in 1992 by the Society of Critical Care Medicine and the American College of Chest Physicians [2]. Since then, SIRS has been defined according to well-established criteria (Table 2.1), without the need for the demonstration of the presence of bacterial infection by microbiological culture, whereas sepsis is considered as a SIRS in response to documented infection that can lead to severe consequences, including multiple organ failure. Table 2.1 SIRS definition requires showing two or more of the following conditions Temperature < 36 °C or > 38 °C Heart rate > 90 beats/min, in absence of pain or anemia Respiratory rate > 20 breaths/min or PaCO2 < 32 mmHg WBC count > 12,000 cells/µL or > 10% immature (band) forms Other stages of sepsis were also defined, such as severe sepsis, associated with organ dysfunction, hypoperfusion or hypotension, and septic shock, the most severe stage of sepsis, cursing with arterial hypotension despite adequate fluid resuscitation. The differentiation between infectious SIRS and other etiologies, as well as the stratification of the disease progression in these three stages, is very important, since their management and evolution are quite different [3]. However, the clinical application of these definitions quickly demonstrated that they lacked sufficient diagnostic efficiency. The presence of clinical signs of inflammation is shown in both infectious and noninfectious processes, microbiological culture being the reference differential diagnostic tool. The development of new biochemical markers of inflammation, such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6), improved the differentiation of both clinical situations, thus allowing the redefinition of SIRS and sepsis in the International Sepsis Definition Conference in 2001 [4]. By this time, a new staging system was established, named PIRO system (from Predisposition, Infection, Response, and Organ Dysfunction) aimed at stratifying patients based on not only the clinical features but also the biochemical markers of inflammation (Fig. 2.1; Ref. [5]). Figure 2.1 Optimum individualized treatment according to PIRO classification of patient's characteristics. From a more clinical perspective, it has been recently proposed to include evidence of organ dysfunction in the criteria for sepsis [6]. Of note, this slightly differs from the definition used in the recently published guidelines of the Surviving Sepsis Campaign in which sepsis is defined clinically as the presence (probable or documented) of infection together with systemic manifestations of infection and severe sepsis is defined as sepsis with sepsis-induced organ dysfunction or tissue hypoperfusion [7]. Despite the great advance in our knowledge on the pathogenesis of sepsis, severe sepsis, defined as sepsis with organ failure, remains associated with an unacceptable high mortality [8]. 2 Immunologic Basis of Sepsis
The inflammatory process starts as a response mediated by cellular and humoral factors that seek to limit, eliminate, and repair the lesion caused by the infectious agent. This inflammatory response is sometimes exaggerated and not limited only to the lesion point, thus spreading to the entire organism and leading to a SIRS. Activating agents, infectious or not, will be recognized by immune system cells by surface receptors (Fig. 2.2; Ref. [9]). SIRS begins with a rapid release of proinflammatory cytokines (IL-1a, IL-1ß, IL-2, IL-6, IL-8, IL-15, IL-18, and a-tumoral necrosis factor or TNF-a), as well as immunological cytokines, ?-interferon, and TNF-ß. Liberation of proinflammatory cytokines is very fast, and they are rapidly cleared from systemic circulation. TNF-a plays a central role in the pathogenesis of SIRS: it is released into peripheral blood...