乌司他丁对于重症脓毒症及脓毒症休克患者血管内皮多糖包被影响的机制研究

发布时间：2018-05-16 20:35

本文选题：重症脓毒症 + 脓毒症休克　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:本研究旨在观察和探讨应用乌司他丁对于重症脓毒症及脓毒症休克患者血管内皮多糖包被的影响。方法:本研究纳入2016年6月至2016年12月河北医科大学第四医院重症医学科由于各种部位感染引发脓毒症甚至脓毒症休克病例。纳入标准包括:1)符合SIRS诊断标准:确诊须具备以下四点中的至少两点:a.体温38℃或36℃、b.心率90次/分、c.呼吸频率20次/分或Pa CO232mm Hg、d.白细胞计数12*109/L或4*109/L(或未成熟粒细胞10%);2)存在可疑或明确感染灶;3)符合重症脓毒症或脓毒性休克诊断标准:(1)重症脓毒症诊断标准:脓毒症所致的组织低灌注或器官功能障碍:a.脓毒症所致低血压;b.乳酸水平超过实验室检测正常水平上限;c.即使给予足够的液体复苏,尿量仍然小于0.5ml/kg/h至少2小时;d.非肺炎所致的急性肺损伤且氧合指数㩳250mm Hg;e.肺炎所致急性肺损伤且氧合指数㩳200mm Hg;f.血肌酐水平㧐2.0mg/d L;g.血胆红素㧐2mg/d L;h.血小板计数㩳100000u L;i.凝血障碍(国际标准化比值㧐1.5);(2)脓毒性休克诊断标准:尽管进行了充分的液体复苏,脓毒症诱发的低灌注仍持续存在。脓毒症诱发的组织低灌注:感染引起低血压、乳酸盐升高或少尿。排除标准:符合下列任意一项者,予以排除:1)糖尿病史;2)年龄18周岁;3)预计住院时间≤24h;4)2周内曾接受化疗治疗;5)孕产妇及哺乳期妇女。于入组0h、24h、72h采集患者临床、实验室指标及生物标志物,主要包括:性别、年龄、入组APACHEⅡ评分,体温、心率、平均动脉压(Mean Arterial Pressure,MAP)、中心静脉压(Central Venous Pressure,CVP);监测白细胞计数(white blood cell count,WBC)、乳酸(Lactate,Lac)、C反应蛋白(C-Reactive Protein,CRP)、降钙素原(Procalcitonin,PCT)、细胞间粘附因子-1(Intercellular Adhesion Molecule,ICAM-1)、多配体蛋白聚糖-1(Syndecan-1,SDC-1)。PICCO监测的患者,同时收集肺毛细血管通透性指数(PVPI)。对患者的预后评估包括:ICU住院天数以及28天病死率。根据是否应用乌司他丁,将患者分为乌司他丁应用组(Y组)、非乌司他丁应用组(N组)。以及APACHE II评分是否大于15分,分别将两组患者分为L15组(APACHE II评分"g15分)、S15组(APACHE II评分㩳15分)。采用SPSS21.0统计软件进行数据处理及分析,符合正态分布的定量资料用(±s)描述,不符合正态分布的定量资料用M(QR)描述,符合正态分布的定量资料的两组间的比较用两独立样本t检验或秩和检验,不同组别率的比较采用卡方检验。结果:1本研究共纳入29名患者,Y组(应用乌司他丁患者)13例:其中L15(APACHE"g15分)组8人,S15(APACHE㩳15分)组5人;N组(非应用乌司他丁患者)16例:其中L15组11人,S15组5人。包括:胸腔感染21例(72.4%)、腹腔感染6例(20.7%)、血流感染1例(3.44%)、泌尿系感染1例(3.44%)。给予乌司他丁应用的患者占总人数的44.8%。2应用乌司他丁对于脓毒症患者多糖包被及预后的影响2.1 Y、N两组患者临床基线特征:Y、N两组患者APACHE II评分、WBC、乳酸、PVPI、PCT、CRP等基线情况无统计学差异(P0.05)。根据入组时采集血标本提示:SDC-1、ICAM-1数据基线情况无统计学差异(P0.05)。证明两组患者均衡可比。2.2 Y、N两组分别经过治疗72h后乳酸水平存在差异,(1.17±0.24vs1.71±0.48mmol/L),差异具有统计学意义(P=0.001)。二者PVPI、SDC-1、ICAM-1均无统计学差异(P0.05)。2.3 Y组患者28天死亡率0,N组患者28天死亡率31%,差异具有统计学意义(P=0.027),二者ICU住院时间无统计学差异(P0.05)。3脓毒症患者APACHE II评分"g15时,应用乌司他丁患者与非乌司他丁应用患者血浆多糖包被水平及预后的比较3.1 L15组中,Y、N两组患者基线特征:Y、N两组患者入组时血标本提示:WBC、乳酸、PCT、CRP、SD C-1以及ICAM-1等基线情况无统计学差异(P0.05)。根据入科6小时内PICCO指标提示:PVPI数据基线情况无统计学差异(P0.05)。证明两组患者均衡可比。3.2 Y、N两组患者经过72h治疗后,乳酸水平存在差异,Y组患者入组72h的乳酸小于N组患者(1.09±0.20vs1.57±0.49mmol/L),差异具有统计学意义(P=0.018),两组患者SDC-1、ICAM-1、PVPI无统计学差异(P0.05)。3.3 Y、N两组患者ICU住院天数、28天病死率无统计学差异(P0.05)。4脓毒症患者APACHE II评分㩳15时,应用乌司他丁患者与非乌司他丁应用患者血浆多糖包被水平及预后的比较。4.1 Y、N两组患者入组时内血标本提示:WBC、乳酸、PCT、CRP、SDC-1、ICAM-1等基线情况无统计学差异(P0.05)。根据入科6小时内PICCO指标提示:PVPI数据基线情况无统计学差异(P0.05)。证明两组患者均衡可比。4.2 Y、N两组患者经72h治疗后,乳酸水平存在差异,(1.3±0.25vs2.02±0.27mmol/L),差异具有统计学意义(P=0.003),Y组患者72h PVPI小于N组患者(4.28±1.75 vs 12.16±4.95%)差异具有统计学意义(P=0.008),Y组72h SDC-1水平小于N组(984.35(711.58)vs3588.30(3872.76)pg/ml),差异具有统计学意义(P=0.049)。Y、N两组患者经治疗后ICAM-1水平无统计学差异(P0.05)。4.3 Y、N两组患者ICU住院天数、28天病死率无统计学差异(P0.05)。5 L15组患者与S15组患者比较,ICAM-1、SDC-1、PVPI基线值不均衡,不可比。结论:1 APACHEⅡ评分反映患者病情危重程度,对于APACHEⅡ评分"g15的脓毒症患者,血管内皮多糖包被结构可能会受到多种因素影响,而考虑到其受损的严重程度,单一药物的作用是有限的。2对于APACHEⅡ评分㩳15的脓毒症患者,乌司他丁应用可能会通过保护血管内皮多糖包被结构,从而改善血管通透性,减少毛细血管渗漏,改善微循环。对于脓毒症患者,乌司他丁应用可能会改善患者死亡率。
[Abstract]:Objective: the purpose of this study was to observe and explore the effects of ulinastatin on vascular endothelial polysaccharides in patients with severe sepsis and septic shock. Methods: This study included cases of sepsis and septic shock caused by various site infections in the fourth hospital of Hebei Medical University from June 2016 to December 2016. Criteria included: 1) compliance with SIRS diagnostic criteria: the diagnosis must have at least two points in the following four points: A. temperature 38 or 36, B. heart rate 90 / min, C. respiratory frequency 20 / min or Pa CO232mm Hg, D. leucocyte count 12*109/L or 4*109/L (or immature granulocyte 10%); 2) suspected or clear infection; 3) conforms to sepsis or septic toxicity. Criteria for diagnosis of shock: (1) diagnostic criteria for severe sepsis: low tissue perfusion or organ dysfunction caused by sepsis: hypotension caused by A. sepsis; B. lactate levels exceeding the upper limit of laboratory tests; C., even if sufficient fluid resuscitation, less than 0.5ml/kg/h at at least 2 hours; and acute lung injury caused by D. non pneumonia And the oxygenation index? 250mm Hg; acute lung injury caused by E. pneumonia and the oxygen index? 200mm Hg; F. blood creatinine level? 2.0mg/d L; g. blood bilirubin? 2mg/d L; h. platelets count; coagulopathy (International standardized ratio? 1.5); (2) septic shock diagnosis standard: although full liquid resuscitation, sepsis induced low perfusion still remains Persistent. Hypoperfusion induced by sepsis: infection caused by hypotension, elevated lactate or oliguria. Exclusion criteria: 1) diabetes history; 2) age 18 years old; 3) hospitalized time less than 24h; 4) received chemotherapy within 2 weeks; 5) pregnant women and lactating women. In group 0h, 24h, 72h collect patients. Clinical, laboratory indicators and biomarkers mainly include: sex, age, APACHE II score in group, body temperature, heart rate, mean arterial pressure (Mean Arterial Pressure, MAP), central venous pressure (Central Venous Pressure, CVP), monitoring white cell count (white blood cell), lactic acid (white blood cell) ) patients with Procalcitonin (PCT), -1 (Intercellular Adhesion Molecule, ICAM-1), multiple ligand proteoglycan -1 (Syndecan-1, SDC-1).PICCO monitoring of the pulmonary capillary permeability index (PVPI). The prognosis of the patients included: the days of hospitalization and the 28 day mortality. The patients were divided into the Ulinastatin application group (group Y), the non Ulinastatin group (group N) and whether the APACHE II score was greater than 15 points, and the two groups were divided into L15 group (APACHE II score "G15), S15 group (APACHE II score 15). The SPSS21.0 statistics software was used for data processing and analysis, which conformed to the quantitative data of normal distribution. (+ s), the quantitative data that did not conform to the normal distribution were described with M (QR). The comparison of the two groups that conformed to the normal distribution of quantitative data was compared with two independent samples t test or rank sum test, and the comparison of the different group rates was checked by Chi square test. Results: 1 subjects included 29 patients and 13 cases of Y (using L15 (APACHE "G15). Group 8, S15 (APACHE? 15) group 5; group N (non use of ulinastatin) 16 cases: group L15 11, S15 group 5. Including: 21 cases of thoracic infection (72.4%), abdominal infection 6 cases (20.7%), blood flow infection (3.44%), urinary tract infection 1 cases (3.44%). Ulinastatin in the total number of patients in the total number of 44.8%.2 application of ulinastatin for sepsis The effect of polysaccharide package and prognosis of 2.1 Y, N two group of patients with clinical baseline characteristics: Y, N two groups, APACHE II score, WBC, lactic acid, PVPI, CRP, and other baseline conditions of no statistical difference (P0.05). Y, N two groups after the treatment of 72h, the level of lactic acid was different, (1.17 + 0.24vs1.71 + 0.48mmol/L), the difference was statistically significant (P=0.001). There were no statistical differences in PVPI, SDC-1, ICAM-1 (P0.05),.2.3 Y group 28 days mortality 0, 28 days of death rate 31%, the difference was statistically significant (two). Statistical difference (P0.05).3 sepsis patients' APACHE II score "G15, using Ulinastatin and non Ulinastatin patients in the plasma polysaccharide packet level and prognosis comparison of the 3.1 L15 group, Y, N two groups of patients baseline characteristics: Y, N two group of blood samples suggest: WBC, lactic acid, PCT, dialectical, and other baseline conditions The study difference (P0.05). According to the PICCO indicator within 6 hours of admission, there was no statistical difference in the baseline of PVPI data (P0.05). It was proved that the balance of the two groups was comparable to that of.3.2 Y. The lactate level in the N two group was different after 72h treatment. The lactic acid in the Y group was less than that of the N group (1.09 + 0.20vs1.57), and the difference was statistically significant. Significance (P=0.018), two groups of patients SDC-1, ICAM-1, PVPI no statistical difference (P0.05).3.3 Y, N two patients with ICU hospitalization days, 28 days of no statistical difference in fatality rate (P0.05).4 septic patient APACHE score score? 15, the use of ulinastatin and non Ulinastatin should be used in patients with plasma polysaccharide package level and prognosis WBC, lactic acid, PCT, CRP, SDC-1, ICAM-1, and other baseline conditions were not statistically significant (P0.05). According to the PICCO index within 6 hours of admission, there was no statistical difference in the baseline of PVPI data (P0.05). It was proved that the balance of the two groups was comparable to.4.2 Y. The levels of lactic acid in the two groups of N two were different (1.3 +. The difference was statistically significant (P=0.003). The difference of 72h PVPI in group Y was less than that of group N (4.28 + 1.75 vs 12.16 + 4.95%), and the 72h SDC-1 level in group Y was less than that of N group (984.35 (711.58) 3872.76), and the difference was statistically significant. Statistical difference (P0.05).4.3 Y, N two patients, ICU hospital days, 28 days of mortality no statistically significant difference (P0.05).5 L15 patients compared with the S15 group, ICAM-1, SDC-1, PVPI baseline values are not equal, no comparable. 1 The structure of the envelope may be affected by a variety of factors, and considering the severity of its damage, the effect of a single drug is a limited.2 for the APACHE II score? 15 of sepsis. The application of ulinastatin may improve vascular permeability, decrease capillary leakage and improve microcirculation by protecting the structure of vascular endothelial polysaccharide package. For patients with sepsis, ulinastatin may improve mortality.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R459.7

【参考文献】