الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Sepsis remains the primary cause of death in intensive care unit (ICU) patients despite improvements in antibiotic and early hemodynamic management. In Europe, sepsis occurrence in acutely ill patients results in an ICU mortality rate ranging between 27 and 54% depending on the severity. In the USA, the Centre for Disease Control estimates that 500,000 people develop sepsis and 200,000 die each year. The prompt diagnosis and assessment of high risk sepsis patients is therefore highly desirable, increasing the possibility of initiating early and specific treatments. Thus, clinical severity scores such as Sequential Organ Failure Assessment (SOFA) score can play a critical role. However, the isolated use of these scoring systems to guide decision-making in sepsis has been heavily criticized. A standardized assessment tool for the early identification of sepsis patients upon admission with a range of severity levels would be of dramatic value in aiding clinical decision-making and optimizing the use of health care resources. Accordingly, a number of prognostic biomarkers have been proposed in the field of sepsis over the last decades many more than in other diseases. Most of these molecules are hormones, cytokines or circulating proteins related to inflammation or the coagulation system and may require considerable time, effort and costs to be measured. Adrenomedullin (ADM) is a peptide which can act as a hormone and is produced by multiple tissues during physiologic and infectious stress with varying physiological functions, including vasodilatory, anti-inflammatory and antimicrobial activity, which is further enhanced by its regulation and modulation of complement activity. Thus, ADM is considered a “hormokine”, characterized by a hormone-like behaviour in non-inflammatory conditions when it is only produced by endocrine cells, and by a cytokine-like behaviour in sepsis when it is ubiquitously hyper-expressed. Moreover, exogenous ADM has been shown to reduce acute lung injury, vascular permeability and death in animal models of sepsis, whilst endogenous over-expression similarly ameliorates the sepsis insult.
Measurement of circulating ADM is complicated by a rapid degradation and clearance from the circulation, and is further masked by a binding protein (complement factor H), preventing its detection by standard immunoassay. The mid-regional fragment of proadrenomedullin (MR-proADM), comprising of amino acids 45–92, is more stable and directly reflects levels of the rapidly degraded active ADM peptide. increased MR-proADM concentrations have been identified in the plasma of patients with community acquired pneumonia (CAP) and are widely used in the risk and severity assessment of this condition. In this study we will compare between serum proadrenomedullin versus SOFA score in day one in prediction of mortality in critically ill septic patients admitted to different units of Alexandria main university hospital ICUs.
The aim of this work is to compare between sensitivity and specificity of serum level of Pro-adrenomedullin versus SOFA score in prediction of mortality during ICU stay days in patient with sepsis and septic shock.
This is across sectional study enrolling 100 consecutive adult male and female patients, who will be admitted to Critical Care Medicine Departments in Alexandria Main University Hospital with the diagnosis of sepsis and septic shock based on definition by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The enrolled patients was adult more than 18 years old and had SOFA score more ≥ 2. We excluded pregnant females patients, patients less than 18 years old, another types of shock (hypovolemic, cardiogenic, obstructive, neurogenic), chronic kidney disease patients and end stage renal disease patients. The absence of a blood sample available for biomarker profiling within the first 24 h following ICU admission, or lack of informed consent. Clinical data recorded from the medical records included demographics, comorbidities, laboratories, microbiology, and biomarker levels. The severity of illness was assessed on admission by calculating the Sequential Organ Failure Assessment (SOFA) score.
Plasma samples for biomarker profiling were collected as close as possible to the moment of ICU admission, and always within the first 24 hour. Study personnel anticoagulated blood samples with heparin and separated plasma by centrifugation within 1 h of collection. The immediately frozen plasma was shipped on dry ice to a central laboratory where it was stored at −80°C then Plasma MR-proADM measurement was performed by TRACE technology (Time Resolved Amplified Cryptate Emission) using a new sandwich immunoassay (Kryptor Compact Plus Analyser, BRAHMS, Hennigsdorf, Germany); limit of detection 0.05 nmol/L.
The pro-adrenomedullin AUC was 0.914 with p value > 0.001 and best cut off point < 7.1 with sensitivity 82.76 and specificity 85.71 with positive predictive value 88.9. As regard SOFA score in day 1 AUC was 0.968 with p value > 0.001 and best cut off point < 9 with sensitivity 84.48 and specificity 95.24 and positive predictive value 96.1. As regard comparison between serum Pro-adrenomedullin vs SOFA score in prediction of mortality in critically ill septic patient, p value for Pairwise comparison between Pro-Adrenomedullin and SOFA day 1 was 0.053 with no significant difference.