烏司他丁對于重癥膿毒癥及膿毒癥休克患者血管內(nèi)皮多糖包被影響的機制研究
發(fā)布時間:2018-05-16 20:35
本文選題:重癥膿毒癥 + 膿毒癥休克 ; 參考:《河北醫(yī)科大學(xué)》2017年碩士論文
【摘要】:目的:本研究旨在觀察和探討應(yīng)用烏司他丁對于重癥膿毒癥及膿毒癥休克患者血管內(nèi)皮多糖包被的影響。方法:本研究納入2016年6月至2016年12月河北醫(yī)科大學(xué)第四醫(yī)院重癥醫(yī)學(xué)科由于各種部位感染引發(fā)膿毒癥甚至膿毒癥休克病例。納入標準包括:1)符合SIRS診斷標準:確診須具備以下四點中的至少兩點:a.體溫38℃或36℃、b.心率90次/分、c.呼吸頻率20次/分或Pa CO232mm Hg、d.白細胞計數(shù)12*109/L或4*109/L(或未成熟粒細胞10%);2)存在可疑或明確感染灶;3)符合重癥膿毒癥或膿毒性休克診斷標準:(1)重癥膿毒癥診斷標準:膿毒癥所致的組織低灌注或器官功能障礙:a.膿毒癥所致低血壓;b.乳酸水平超過實驗室檢測正常水平上限;c.即使給予足夠的液體復(fù)蘇,尿量仍然小于0.5ml/kg/h至少2小時;d.非肺炎所致的急性肺損傷且氧合指數(shù)㩳250mm Hg;e.肺炎所致急性肺損傷且氧合指數(shù)㩳200mm Hg;f.血肌酐水平㧐2.0mg/d L;g.血膽紅素㧐2mg/d L;h.血小板計數(shù)㩳100000u L;i.凝血障礙(國際標準化比值㧐1.5);(2)膿毒性休克診斷標準:盡管進行了充分的液體復(fù)蘇,膿毒癥誘發(fā)的低灌注仍持續(xù)存在。膿毒癥誘發(fā)的組織低灌注:感染引起低血壓、乳酸鹽升高或少尿。排除標準:符合下列任意一項者,予以排除:1)糖尿病史;2)年齡18周歲;3)預(yù)計住院時間≤24h;4)2周內(nèi)曾接受化療治療;5)孕產(chǎn)婦及哺乳期婦女。于入組0h、24h、72h采集患者臨床、實驗室指標及生物標志物,主要包括:性別、年齡、入組APACHEⅡ評分,體溫、心率、平均動脈壓(Mean Arterial Pressure,MAP)、中心靜脈壓(Central Venous Pressure,CVP);監(jiān)測白細胞計數(shù)(white blood cell count,WBC)、乳酸(Lactate,Lac)、C反應(yīng)蛋白(C-Reactive Protein,CRP)、降鈣素原(Procalcitonin,PCT)、細胞間粘附因子-1(Intercellular Adhesion Molecule,ICAM-1)、多配體蛋白聚糖-1(Syndecan-1,SDC-1)。PICCO監(jiān)測的患者,同時收集肺毛細血管通透性指數(shù)(PVPI)。對患者的預(yù)后評估包括:ICU住院天數(shù)以及28天病死率。根據(jù)是否應(yīng)用烏司他丁,將患者分為烏司他丁應(yīng)用組(Y組)、非烏司他丁應(yīng)用組(N組)。以及APACHE II評分是否大于15分,分別將兩組患者分為L15組(APACHE II評分"g15分)、S15組(APACHE II評分㩳15分)。采用SPSS21.0統(tǒng)計軟件進行數(shù)據(jù)處理及分析,符合正態(tài)分布的定量資料用(±s)描述,不符合正態(tài)分布的定量資料用M(QR)描述,符合正態(tài)分布的定量資料的兩組間的比較用兩獨立樣本t檢驗或秩和檢驗,不同組別率的比較采用卡方檢驗。結(jié)果:1本研究共納入29名患者,Y組(應(yīng)用烏司他丁患者)13例:其中L15(APACHE"g15分)組8人,S15(APACHE㩳15分)組5人;N組(非應(yīng)用烏司他丁患者)16例:其中L15組11人,S15組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%)。給予烏司他丁應(yīng)用的患者占總?cè)藬?shù)的44.8%。2應(yīng)用烏司他丁對于膿毒癥患者多糖包被及預(yù)后的影響2.1 Y、N兩組患者臨床基線特征:Y、N兩組患者APACHE II評分、WBC、乳酸、PVPI、PCT、CRP等基線情況無統(tǒng)計學(xué)差異(P0.05)。根據(jù)入組時采集血標本提示:SDC-1、ICAM-1數(shù)據(jù)基線情況無統(tǒng)計學(xué)差異(P0.05)。證明兩組患者均衡可比。2.2 Y、N兩組分別經(jīng)過治療72h后乳酸水平存在差異,(1.17±0.24vs1.71±0.48mmol/L),差異具有統(tǒng)計學(xué)意義(P=0.001)。二者PVPI、SDC-1、ICAM-1均無統(tǒng)計學(xué)差異(P0.05)。2.3 Y組患者28天死亡率0,N組患者28天死亡率31%,差異具有統(tǒng)計學(xué)意義(P=0.027),二者ICU住院時間無統(tǒng)計學(xué)差異(P0.05)。3膿毒癥患者APACHE II評分"g15時,應(yīng)用烏司他丁患者與非烏司他丁應(yīng)用患者血漿多糖包被水平及預(yù)后的比較3.1 L15組中,Y、N兩組患者基線特征:Y、N兩組患者入組時血標本提示:WBC、乳酸、PCT、CRP、SD C-1以及ICAM-1等基線情況無統(tǒng)計學(xué)差異(P0.05)。根據(jù)入科6小時內(nèi)PICCO指標提示:PVPI數(shù)據(jù)基線情況無統(tǒng)計學(xué)差異(P0.05)。證明兩組患者均衡可比。3.2 Y、N兩組患者經(jīng)過72h治療后,乳酸水平存在差異,Y組患者入組72h的乳酸小于N組患者(1.09±0.20vs1.57±0.49mmol/L),差異具有統(tǒng)計學(xué)意義(P=0.018),兩組患者SDC-1、ICAM-1、PVPI無統(tǒng)計學(xué)差異(P0.05)。3.3 Y、N兩組患者ICU住院天數(shù)、28天病死率無統(tǒng)計學(xué)差異(P0.05)。4膿毒癥患者APACHE II評分㩳15時,應(yīng)用烏司他丁患者與非烏司他丁應(yīng)用患者血漿多糖包被水平及預(yù)后的比較。4.1 Y、N兩組患者入組時內(nèi)血標本提示:WBC、乳酸、PCT、CRP、SDC-1、ICAM-1等基線情況無統(tǒng)計學(xué)差異(P0.05)。根據(jù)入科6小時內(nèi)PICCO指標提示:PVPI數(shù)據(jù)基線情況無統(tǒng)計學(xué)差異(P0.05)。證明兩組患者均衡可比。4.2 Y、N兩組患者經(jīng)72h治療后,乳酸水平存在差異,(1.3±0.25vs2.02±0.27mmol/L),差異具有統(tǒng)計學(xué)意義(P=0.003),Y組患者72h PVPI小于N組患者(4.28±1.75 vs 12.16±4.95%)差異具有統(tǒng)計學(xué)意義(P=0.008),Y組72h SDC-1水平小于N組(984.35(711.58)vs3588.30(3872.76)pg/ml),差異具有統(tǒng)計學(xué)意義(P=0.049)。Y、N兩組患者經(jīng)治療后ICAM-1水平無統(tǒng)計學(xué)差異(P0.05)。4.3 Y、N兩組患者ICU住院天數(shù)、28天病死率無統(tǒng)計學(xué)差異(P0.05)。5 L15組患者與S15組患者比較,ICAM-1、SDC-1、PVPI基線值不均衡,不可比。結(jié)論:1 APACHEⅡ評分反映患者病情危重程度,對于APACHEⅡ評分"g15的膿毒癥患者,血管內(nèi)皮多糖包被結(jié)構(gòu)可能會受到多種因素影響,而考慮到其受損的嚴重程度,單一藥物的作用是有限的。2對于APACHEⅡ評分㩳15的膿毒癥患者,烏司他丁應(yīng)用可能會通過保護血管內(nèi)皮多糖包被結(jié)構(gòu),從而改善血管通透性,減少毛細血管滲漏,改善微循環(huán)。對于膿毒癥患者,烏司他丁應(yīng)用可能會改善患者死亡率。
[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.
【學(xué)位授予單位】:河北醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R459.7
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