Tóm tắt Luận án Research value of presepsin in diagnos is and prognos is of severe sepsis and septic shock patients

Nội dung tài liệu: Tóm tắt Luận án Research value of presepsin in diagnos is and prognos is of severe sepsis and septic shock patients

1. MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENCE SCIENTIFIC RESEARCH INSTITUTE OF CLINICAL MEDICINE 108 -------------------- NGUYỄN VIẾT QUANG HIỂN RESEARCH VALUE OF PRESEPSIN IN DIAGNOSIS AND PROGNOSIS OF SEVERE SEPSIS AND SEPTIC SHOC K PATIENTS Specialism: Aneathesia and resuscitation Code: 62720122 MEDICAL DOCTORAL THESIS Hà Nội, 2019
2. Science Instructors: 1. Ass.Prof. PhD Le Thi Viet Hoa 2. Ass.Prof. PhD Nguyen Phuong Dong Opponent 1: . Opponent 2: . Opponent 3: . The thesis has been defended at University-level Thesis Evaluation Council held in Scientific research Institute of clinical medicine 108 At, ...... ...... (hour), ...../...../2019 (date) This thesis may be found at: - National Library - Library of Scientific research Institute of clinical medicine 108
3. 1 INTRODUCTION 1. The urgency of thesis Septic shock is an acute circulatory failure that reduces the perfusion of organs, promotes systemic inflammatory response and prolonged metabolic disorders, leading to multiple organ failure and death. Early identification and effective management reduce mortality in septic shock. Biomarkers have an important role in diagnosis as well as prognosis of septic shock. Currently there are many biomarkers that help diagnose and prognosis patients with septic shock such as CRP, PCT, presepsin ... Presepsin is a soluble molecule of CD14, created when the body responds to infection. Many studies show that presepsin is valuable in early diagnosis (up to 2 hours after infection) sepsis and septic shock. Some meta-analyzes have demonstrated that presepsin has better value than PCT in the diagnosis and prognosis of sepsis and septic shock. In Vietnam, no studies to evaluated the role of plasma presepsin in diagnosis and prognosis sepsis and septic shock. 2. The meaning of thesis The thesis contributes new to theory and practice of using biomarkers presepsin in the direction of diagnosis and prognosis in patients with severe sepsisand septic shock, thereby allowing the use of presepsin as a tool. diagnosis, monitoring and prognosis for patients with severe sepsisand septic shock. This is the first study in Vietnam. 3. Objectives - Evaluate concentration changes and the role of plasma presepsin in diagnosing severe sepsisand septic shock. - Determine the correlation of plasma presepsin with some scales and biomarkers assessing the severity in prognosis of mortality on patients with severe sepsis and septic shock.
4. 2 4. Structure of thesis The thesis has 112 pages including 2 pages of introduction and objectives, 35 pages of overview, research subjects and methods 22 pages, results 22 pages, discussion 22 pages, conclusions and recommendations 3 pages. The thesis has 27 tables, 10 pictures and 11 charts. The thesis uses 134 references, in which 13 Vietnamese documents, 121 English documents, 03 articles related to the topic have been published.
5. 3 Chapter 1 :OVERVIEW 1.1. Septic shock In 1991, the first consensus conference between the American College of Chest Physicians and the Society of Critical Care Medicine agreed to provide the following definitions of sepsis, severe sepsis and septic shock: Infection: A bacterial infection characterized by a local inflammatory response to microorganisms (bacteria, viruses, fungi, and parasites) or invasion of sterile tissue by these microorganisms. Systemic Inflammatory Reponse Syndrome (SIRS): is a global inflammatory response for many different agents characterized by the presence of at least 2 of the following criteria: - Body temperature> 380C or <360C; - Heart rate> 90 times / minute; - Breathing frequency> 20 times / minute or PaCO2 <32 mmHg; - The number of peripheral blood leukocytes> 12G / L or <4G / L or leukocytes accounts for> 10%. - Septicemia (sepsis): Systemic inflammatory response syndrome + Positive infection or blood culture positive. Severe sepsis: sepsis conditions that manifest organ dysfunction, hypofusion or hypotension. Septic shock is a serious infection with prolonged hypotension (systolic blood pressure <90 mmHg or a decrease of more than 40 mmHg compared to the initial blood pressure of the patient) and does not respond with fluid replacement. In 2001, the consensus conference between the Society of Critical Care Medicine and the European Society of Intensive Care Medicine proposed adding diagnostic criteria to the definitions but did not provide alternative definitions because it have not enough evidence.
6. 4 In 2016, European and American resuscitation experts agreed to make new updates on infection definition with four main points: - Agree to remove the term "severe sepsis" because the word "sepsis" itself means a serious infection. - Sepsis is defined as a life-threatening organ dysfunction due to an uncoordinated response to infection. - Diagnosis of septic shock when the patient meets the criteria for sepsis, even though the circulating volume is sufficient but still requires vasopressors to maintain the mean blood pressure ≥ 65 mmHg and accompanied by increasing the lactate serum> 2 mmol / l. - The conference agreed not to use systemic inflammatory response syndrome in the diagnosis of sepsis and septic shock but instead replaced with qSOFA scale and SOFA. 1.2. Role of presepsin in infection 1.2.1. The origin and structure of presepsin Presepsin (sCD14-ST) is a 13 kDa peptide created by soluble protein hydrolysis of the cluster of differentiation CD14 (sCD14). There are 2 forms of soluble CD14 in plasma of healthy people with very low concentrations including molecules weighing 49 KDa and 55 KDa. sCD14 plays an important role in mediating immune response to LPS of cells without clustering CD14 such as endothelial and epithelial cells. 1.2.2. Kinetics of presepsin Presepsin concentration increased within 2 hours after bacterial infection, peaked after 3 hours. This feature makes presepsin molecule become the biomarker that responds quickly to infection when compared with PCT and CRP with activation time of 6-12 hours and 12-24 hours, respectively. Plasma half-life is 4-5 hours, compared with 12-24 hours for PCT, allowing early evaluation as well as treatment efficacy. Presepsin is mainly excreted by the kidneys.
7. 5 1.2.3. Value of plasma presepsin in infection Presepsin is a new biomarker who plays a role in early identification of sepsis and is valuable in the prognosis of severity and mortality in patients with severe sepsis and septic shock. 1.2.4. Studies on plasma presepsin in infections on global and Vietnam - Research on the concentration and role of plasma presepsin in diagnosing severe sepsis and septic shock. - Research on the role of plasma presepsin in prognosis of patients with severe sepsis and septic shock. - In Vietnam, presepsin has also been used in diagnosing infections in some hospitals such as Hue Central Hospital ... However, there has not been any specific study evaluating the role of plasma presepsin in diagnosis as well as prediction patients with severe sepsis and septic shock. Chapter 2 MATERIALS AND METHO D 2.1. Materials: research on 80 patients with severe sepsis and septic shock treated in anesthesia Department of Anesthesia A - Hue Central Hospital from 01/2015 to 01/2017. 2.1.1. Criteria for selecting: Patients> 18 years old, having sufficient evidence to diagnose severe sepsis and shock with American College of Chest Physicians and the Society of Critical Care Medicine standard (2001). 2.1.2. Exclusion criteria: Patients or family members do not agree to participate in the study, patients with malignancy, HIV infection, immunosuppressive drugs, end-stage chronic renal failure. 2.1.3. Standard type out of the study: Patients who are eligible for admission to study but must end treatment because the patient's fam ily wishes.
8. 6 2.2. Research methodology. 2.2.1. Study design: Prospective study, cross-sectional description, vertical monitoring and comparison with control group. 2.2.2. Calculating example size According to research by Ali (2016) [15], prognostic mortality value of presepin's is 0.89. We choose the current mortality rate of severe sepsis and septic shock based on the study of Tran Xuan Thinh (2016) [11] of 31%. n = (FP + TN)/(1-p)= 37,6/0,69 = 54,5 In summary, we need sample size> 55 patients to meet the requirements of the research goal 2.2.3. Research devices - Multi-functional hemodynamic monitoring system - Blood gas machine, Cardiopulmonary X-ray machine in bed - Presepsin kit 2.2.4. Evaluation criteria 2.2.4.1. Evaluation criteria for 2 study objectives The evaluation criteria for objective 1: assessing the concentration change and the role of plasma presepsin in diagnosing severe sepsis and septic shock. - Plasma presepsin concentration in patients with severe sepsis and septic shock. + Determination of plasma presepsin concentration at the study time: presepsin concentration right after diagnosis of severe sepsis and septic shock (T0), after 24 hours (T1) and after 7 days (T7). + Change the plasma presepsin concentration by age, sex, bacterial culture results (negative or positive) at the time of study.
9. 7 + Determination of changes in plasma presepsin concentrations at the study time between the living and death groups. - Value of plasma presepsin in differential diagnosis of severe sepsisand septic shock. + Compare presepsin, PCT and CRP concentrations at T0 between severe sepsis and septic shock groups + Analysis of ROC curves of presepsin compared with PCT and CRP in differential diagnosis between severe sepsis and septic shock The evaluation criteria for objective 2: determining the correlation of plasma presepsin with the severity score in the prognosis of mortality in patients with severe sepsisand septic shock - Evaluate the correlation of presepsin, PCT and CRP with severity scales in patients with severe sepsis and septic shock + Determining the correlation between presepsin, PCT and CRP with severity scales (APACHE II, SOFA, SAPS 2, MODS). + Determine the correlation between presepsin, PCT and CRP with plasma lactate. - Determine the mortality prognostic value of plasma presepsin in patients with severe sepsis and septic shock. + Analysis of ROC curve in presepsin mortality prognosis at the time of study. + Analyzing the ROC curve in presepsin’s mortality prognosis at time T0 compared with APACHE II, SOFA, SAPS 2 and MODS scale. + Analysis of the ROC curve in presepsin mortality prognosis in combination with the severity scales (SOFA, APACHE II, SAPS 2, MODS) at time T0 compared to presepsin alone. + Analyzing the ROC curve in presepsin mortality prognosis compared to the biomarkers of PCT, CRP and lactate at the time of T0. + Multivariate regression analysis to identify independent risk factors in mortality prognosis in patients with severe sepsis and septic shock.
10. 8 2.2.4.2. Other evaluation criteria - Determine general characteristics of age, gender, bacteria access path, circulation, rating scale - Describe characteristics of hematological testing, liver, kidney, blood sugar, lactate, blood gas, IL-6, microbiological characteristics. - Treatment results (number of days resuscitation, mechanical ventilation rate, mechanical ventilation time, rate and death) 2.2.4. Study procedure 2.2.4.1. The time of conducting research - Time T0: time of diagnosis of severe sepsis and septic shock. - Time T1: 24 hours after diagnosis of severe sepsis and septic shock. - Time T7: 7 days after diagnosis of severe sepsis and septic shock. 2.2.4.2. Acquiring patients into the study: Patients who are eligible for diagnosis or are eligible for inclusion in the control group are enrolled in the study after obtaining the consent of the patient, or the patient's family members if the patient is not alert . 2.2.5.3. Prepare research sheets for each patient 2.2.5.4. Applying a treatment regimen for severe sepsis and septic shock according to SSC 2012 guidelines 2.2.5.5. Monitor and record research parameters - Continue to monitor and treat patients daily. The clinical symptoms were recorded and the presepsin, PCT, IL-6 and lactate tests were performed at times T0 (diagnosis time), T1 (after 24 hours) and T7 (after 7 days). - Monitor patients' response to treatment, record treatment results such as mechanical ventilation time, resuscitation period, hospital stay. - Patients who die: are patients who die in hospitals or patients who are too heavy to be sent home. 2.3. Data processing: The data are processed according to the medical statistical calculations, SPSS software 20.0