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The Functional Evaluation of Organs in Children with Severe Sepsis and the Value of NT-Pro BNP in Early Essenssing of Their Cardiovascular Function

Author: LiMin
Tutor: YuYongHui
School: Shandong University
Course: Clinical
Keywords: severe sepsis multiple organ disfunction syndrome disseminatedintravascular coagulation N-terminal pro brain natriuretic peptide
CLC: R720.597
Type: Master's thesis
Year: 2012
Downloads: 133
Quote: 1
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Abstract


Background and objective:A series of researches proved that sepsis, a kind of infection, caused serious systemic inflammatory response syndrome (SIRS). Its symptoms were induced by the body’s defense system, not by the invading pathogens. Most patients died eventually not from the original disease of infection, but from multiple organ disfunction syndrome (MODS) induced by sepsis. MODS was a kind of clinical syndrome which refered to two or more systems or organs dysfunction/failure (cardiovascular, respiratory, nerve, blood, kidney, liver, gastrointestinal tract) at the same time or sequentially, which occurred during24hours after acute damage, suck as severe trauma, shock, infection or major operation. In other words, the patients’ multiple organ function alterated after acute injury so that couldn’t maintain body homeostasis stability. Clinically, the functional evaluation of every organ was the highlights in the diagnosis and treatment of sepsis, and the prompt and effective symptomatic treatment could reverse sequential multiple organ involvement and death, so that changed the patient’s prognosis fundamentally.In the early phase of severe sepsis, the cardiovascular function often involved firstly. But this cardiovascular functional disorder often was lack of typical early clinical symptoms, so a specific, sensitive biological marker was needed to assess the cardiovascular functional condition earlier and dynamically. Plasma N-terminal pro brain natriuretic peptide (NT-pro BNP) as a new laboratory test index, was widely used as a specific biological marker for the detection of cardiovascular functional disorder and the diagnosis of heart failure in recent years clinically. Recent research showed that NT-pro BNP also had some corresponding change in severe sepsis.In this study, we evaluated the functional condition of several organs in children with severe sepsis comprehensively and dynamically, and discussed the dynamic chang rule of multiple organ involved, clinical assessment methods and their effective intervention measures. At the same time, serum NT-Pro BNP was detected in children with severe sepsis and the relationship between NT-Pro BNP and the cardiovascular functional condition and the prognosis was analyzed by correlation analysis. The value of NT-Pro BNP as a specific biological marker early indicating the cardiovascular disfunction was assessed in children with severe sepsis.MethodsThe descriptive data case control study method was used in this clinical study. The data of all the cases was collected prospectively. The starting point was that time on which children were admitted to the hospital, and the end point as death or discharge. Factors examined included age, gender, underlying diseases, the primary site of infection, the number and extent of MODS for involved organs, the markers of acute inflammatory response, the pathogen detection [Mycoplasma pneumoniae antibody (MP-IgM), blood/pleural fluid culture, blood/urine EB virus DNA, cytomegalovirus-DNA (CMV-DNA), EB virus antibody-IgM], bone marrow examination, chest high resolution CT (HRCT), diffusion weighted imaging (DWI) of head. Eventually, the clinical materials were inputed into EXCEL to establish database for statistical analysis.After admission. Pediatrics critical illness score (PCIS) and Glasgow coma score were completed immediately. The following laboratory tests were detected, including the peripheral blood routine detection, C-reactive protein (CRP), procalcitonin (PCT), erthrocyte sedimentation rate (ESR), makers of myocardial damage of cardiac troponin T (cTnT). creative kinase isoenzyme (CKMB), myoglobin. NT-Pro BNP, liver function, caogulation function, pathogenic detection (MP-IgM, the blood/pleural effusion culture, blood/urine EB virus DNA, CMV-DNA, EB virus antibody). Arterial blood gas analysis was determined, the lacticacid (Lac), base excess (BE), partial pressure of oxygen (PO2), partial pressure of cabon dioxide (PCO2), calculation of the oxygenation index (PO2/FO2). Bone marrow cytology was done when the peripheral blood neutrophils absolute value (NEUT) was≤0.5×10and/or platelet<80×109and/or hemoglobin<70g/L. The cerebrospinal fluid examination was completed while the patients had nervous system involvement symptoms. Electrocardiogram (ECG), chest HRCT, abdominal X-ray, abdominal ultrasound, echocardiography (UCG), brain DWI and other auxiliary examination were completed according to the patients’condition.All the113children with severe sepsis were divided into two groups of the Survival Group and the Death Group according to their prognosis. As for the32cases completed the detection of serum NT-Pro BNP level, they were also divided into the Survival Group and the Death Group according to their prognosis; and at the same time thet were divided into NT-Pro BNP Normal Group and NT-Pro BNP Increasing Group according to their NT-Pro BNP level increasing or not.Results:1.113cases with severe sepsis were incorporated in this study, in which76cases were male,37cases were female;91cases cure/improvement (cure/improvement rate was80.53%),22cases died (the mortality was19.47%). The fundamental cause of death included disseminated intravascular coagulation (DIC)/important organ hemorrhage in8cases (36.36%), circulatory failure in8cases (36.36%), herniation/brain death in3cases (13.64%) and acute fulminant hepatic failure in3cases (13.64%).2. In all the113cases of severe sepsis in children.55cases (48.67%) occurred cardiovascular dysfunction,55cases (48.67%) occurred hematopoietic dysfunction,54cases (46.02%) occurred liver dysfunction,39cases (34.51%) developed gastrointestinal dysfunction.32cases (28.32%) showed neurological dysfunction, and20cases (17.70%) occurred kidney dysfunction.3.58cases (51.33%) occured early microcirculatory impairment, none case developed circulatory failure after accepting positive "early goal directed therapy" (EGDT) without fluid resuscitation;55cases (48.67%) showed capillary leak syndrome (CLS), and CLS were corrected after active application of hydroxyethyl starch for " plugging" for3~7d;44cases accepted bone marrow cytology, all (100%) showed different hematopoietic function involvement of bone marrow;91cases (80.53%) occurred coagulation dysfunction, including74cases (65.49%) with Pre-DIC,23cases (20.35%) with DIC, wherein8cases died (36.36%) for important organ hemorrhage;26cases (23%) developed infection-associated hemophagocytic syndrome (HLH), in which7cases’bone marrow cytology revealed histiocytic hyperplasia and their pathogen detection confirmed as EB virus infection;42cases (84.62%) occurred acute respiratory distress syndrome (ARDS)/acute lung indury (ALI)/I type respiratory failure, and none case died eventually due to respiratory failure after giving the noninvasive/invasive respiratory support; Liver function involvement also showed hypoalbuminemia in71cases (62.83%), APTT and/or PT significantly prolonged in40patients (74.07%), acute fulminant hepatic failure in3cases (5.56%); Function of gastrointestinal tract involvement,26cases (23.01%) were younger than1year of age, and their performance was paralytic intestinal obstruction in15cases (57.69%), peritoneal cavity empyema in6cases (23.08%), intra-abdominal hypertension in9cases (34.62%), all the children (100%) had feeding intolerance, and13cases (11.50%) elder than1year of age, performed stress ulcer and gastrointestinal bleeding in12cases (10.62%), reactive cholecystitis in4cases (3.54%);27cases (23.89%) were diagnosed as gut-derived sepsis, in which10cases (37.04%) were confirmed with congenital digestive tract malformation.4. The main risk factors closely related to the prognosis of severe sepsis in children were age≤1y (x2=4.589, P<0.05), presence of underlying disease (x2=10.225, P<0.05), primary intra-abdominal infection (x2=6.367, P<0.05), mean arterial pressure (Mean arterial pressure. MAP)(t=2.059, P<0.05), capillary refill time (t=-4.862. P<0.05), the serum Lac (t=-67.162, P<0.05), PCT (t=3.632, P<0.05), PLT count (t=0.171, P<0.05), the number of involved organs (t=-7.018, P<0.05), hypoalbuminemia (x2=26.675, P<0.05), hypoglycemia (x2=3.934, P<0.05); When there were multiple organ dysfunction, the mortality rate increased remarkably with the increase of the number of involved organs.5.32cases of severe sepsis completed the detection of serum NT-Pro BNP level, in which18cases were male,14cases were female;22cases (76.67%) showed NT-Pro BNP increasing, and other10cases (31.25%) had the normal NT-Pro BNP level;26cases cure/improvement (cure/improvement rate was81.25%),6cases died (the mortality was18.75%). Compared with that in the healthy control group, serum NT-Pro BNP (t=2.556, P<0.05), CKMB (t=1.689, P<0.05) and cTnT (t=1.876, P <0.05) level elevated significantly in the severe sepsis group, while there was no significant difference between the two groups for their myoglobin (t=1.133, P>0.05), left ventricle eject fraction (LVEF)(t=1.243, P>0.05) and left ventricular end-diastolic volume index (LVEDVI)(t=1.304, P>0.05).6. In32children with severe sepsis, there was significant difference between the survival group and the death group for their serum NT-Pro BNP (t=2.753, P<0.05), cTnT (t=4.805, P<0.05), BE (t=3.163, P<0.05), serum Lac (t=11.060, P<0.05), capillary refill time (t=5.443, P<0.05) and MAP (t=1.705, P<0.05). Meanwhile, there was also significant difference between the normal NT-Pro BNP groupand the elevated NT-Pro BNP group for their PCIS (t=3.043, P<0.05), time of the mechanical ventilation (t=2.543, P<0.05), vasoactive drugs application proportion (χ2=4.351, P <0.05), vasoactive drugs application time (t=2.343, P<0.05), time in PICU (t=2.674, P<0.05) and the mortality rate (χ2=4.542, P<0.05). Correlation analysis showed that NT-pro BNP level was positively correlated with PCIS score (r=0.321, P<0.05), vasoactive drugs application ratio (r=0.542, P<0.05), vasoactive drugs application time (r=0.875, P<0.05), while was negatively correlated with MAP (r=-0.763, P<0.05) and the mortality rate (r=-0.568, P<0.05). Correlation analysis showed that there was no obvious correlation between cTnT and CKMB with the above parameters, P>0.05.Conclusions:1. In children with severe sepsis, the organs involved incidence followed by hematopoietic function, cardiovascular function, liver function, respiratory function, gastrointestinal function, neurological function and renal function sequentially. The current standard of evaluation for every organ function in the diagnosis and treatment of sepsis is not comprehensive. More attention should be paid to the correct and comprehensive assessment for every organ function so as to aplly earlier anticipatory treatment.2. When the children with sepsis occurred with multiple organs dysfunction, the mortality rate increased significantly with the increase of the number of involved organs. When the children occurred with decompensated circulatory failure, DIC/important organ hemorrhage and acute fulminant liver failure, the prognosis was poor.3. The prognosis of severe sepsis was closely related to the following factors such as age≤1y, presence of underling diseases, primary gastrointestinal tract infection, mean arterial pressure, capillary refill time, serum Lac, PCT, PLT count, the number of the involved organs, hypoalbuminemia and hypoglycemia.4. For children with severe sepsis, the plasma NT-Pro BNP level was sensitive and specific to suggest their cardiovascular function involvement, and was related to the patients’ prognosis. So the plasma NT-Pro BNP levels could be an early specific biological marker for cardiovascular function involved in children with severe sepsis.

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