老年住院患者肠外营养相关性肝损害影响因素研究

发布时间：2018-04-27 15:01

本文选题：老年住院患者 + 肠外营养相关性肝损害　；参考：《山东大学》2017年硕士论文

【摘要】：研究背景我国已步入老龄化社会,且老龄化进程在逐步加快。第六次人口普查结果显示,我国65岁及以上人口近1.2亿,占总人口的8.87%,同2000年相比,65岁及以上老龄人口的比重上升了 1.91个百分点。随着老龄人口的不断增加,老年住院患者得到越来越多的关注,且由于老年疾病的特殊性和复杂性,使得其相关研究更具特殊意义。研究发现,老年住院患者更容易发生营养不良及相关疾病,而营养支持是解决营养不良及其相关疾病问题的重要手段,但其伴随的并发症亦引起重视。肠外营养相关性肝损害(parenteral nutrition associated liver disease,PNALD)是肠外营养支持(parenteral nutrition,PN)常见的严重并发症之一。其病因多样,包括胃肠道基础性疾病、胆汁酸肠肝循环障碍、脓毒血症、菌群失调等,但其发病机制尚待进一步研究,目前比较集中的观点是脂质影响、肠道损伤和营养失衡。PNALD的预防治疗,针对其病因及可能的发病机制,主要围绕减轻脂质影响、调节肠道菌群、保护肠道屏障、减少脓毒血症、通畅胆汁引流等方面进行。双歧杆菌是人体肠道正常菌群中的优势菌种之一,对保护肠屏障、减轻菌群异位及脓毒血症有积极意义,其对肝功能的保护也日益得到重视。有研究在PNALD模型中发现双歧杆菌在防治PNALD中发挥有益的作用,但其在成人及老年人PNALD中尚缺乏相关研究。熊去氧胆酸(UDCA)能够增加胆汁酸的分泌,促进胆汁排出,降低胆红素,对于新生儿由于长期PN引起的胆汁淤积有显著疗效,但其在成人及老年人PNALD中的研究尚不多见。研究目的1.调查老年住院患者肠外营养支持情况,评估营养支持前后肝功能指标变化情况,分析老年住院患者肠外营养支持现状及PNALD发生情况。2.分析相关影响因素(年龄、性别、营养支持方式、时间、总热能、非蛋白质热能、药物)对PNALD的影响,探寻更合理的营养支持方案。3.探讨营养支持联合双歧杆菌治疗对肝功能的影响及PNALD发生率,为临床用药提供参考。4.探讨营养支持联合UDCA治疗对肝功能的影响及PNALD发生率,为临床用药提供参考。研究方法回顾性分析2012年5月至2016年10月山东大学齐鲁医院老年病科171例肠外营养支持患者归档病历。1.研究对象:年龄≥65岁,肠外营养支持≥7d,至少有营养支持前、后的肝功能指标各一次,且营养支持前的肝功能指标无明显异常,并排除肝损害的其他病因。共纳入171例。2.资料收集:收集并统计研究对象的一般情况、营养支持情况、营养支持前的肝功能指标(为距离营养支持开始时间最近指标)、营养支持后的肝功能指标(为距离营养支持结束时间最近指标)、双歧杆菌或UDCA应用情况。3.研究设计:(1)分析研究对象一般情况及营养支持情况,比较不同营养支持情况下PNALD的发生情况;(2)将研究对象分为PNALD和肝功能正常组,对比分析不同研究组之间年龄、性别、营养方案、营养支持时间等的差异,探讨相关因素对PNALD的影响;(3)将研究对象分为双歧杆菌组、UDCA组和对照组(未联合双歧杆菌及UDCA),对比分析不同研究组之间营养支持前、后肝功能指标变化情况,比较PNALD的发生率,探讨药物对PNALD预防的有效性。4.统计学方法:采用Excel 2007、SPSS 21.0及GraphPad Prism 5进行统计学分析及图表绘制。计量资料用均数±标准差(x±s)表示,符合正态分布资料用方差分析和t检验比较组间差异,不符合正态分布资料用非参数检验比较组间差异。计数资料用例数和百分比表示,用卡方检验分析比较组间差异;各组例数小于5的资料的用Fisher's精确概率进行检验。对PNALD影响因素的多元统计学分析,使用logistic多元回归分析进行检验。以α=0.05为检验标准,P0.05表示差异有统计学意义。结果1.研究对象基本资料共有171例老年住院患者纳入本次研究,平均年龄为(79.45±7.44)岁,其中包括男性114例(66.67%),平均年龄(80.06±7.36)岁,女性57例(33.33%),平均年龄(78.23±7.51)岁。不同性别患者在年龄、胃肠道疾病的比较上,差异无统计学意义(p0.05),见表1。2.肠外营养支持情况及PNALD发生情况171例研究对象中有53例(30.99%)接受了完全肠外营养(total parenteral nutrition,TPN)治疗,平均营养支持时间(15.47±5.31)天,平均总热量(20.72±4.63)kcal/kg/d,平均非蛋白质热量(16.20±4.42)kcal/kg/d;接受肠外联合肠内营养(enteral nutrition,EN)治疗的有118例(69.01%),平均营养支持时间(14.86±5.46)天,平均总热量(21.72±8.74)kcal/kg/d,平均非蛋白质热量(17.51±7.95)kcal/kg/d。接受不同营养支持方式治疗患者的营养支持时间、平均总热量及平均非蛋白质热量差异均无统计学意义(p0.05),见表2。171例研究对象中发生PNALD的有34例(19.88%),53例接受TPN患者中发生PNALD的有16例(30.19%),118例接受PN联合EN治疗患者中发生PNALD的有18例(15.25%),接受不同营养支持方式治疗患者PNALD的发生率差异有统计学意义(p0.05),见表 3。3.PNALD影响因素分析将研究对象分为PNALD组(n=34)和肝功能正常组(n=137)。两组患者治疗前基本情况及肝功能指标见表4。两组研究对象之间年龄、性别、胃肠道疾病均无统计学差异(p0.05),肝功能指标均在正常范围。两组研究对象之间营养支持方式、营养支持时间、营养支持总热量、营养支持非蛋白质热量、药物差异均有统计学意义(p0.05),见表5。将上述有统计学差异的影响因素进行二元logistics回归分析,结果见表6。营养支持方式的偏回归系数为-0.967,差异有统计学意义(p0.05)。营养支持时间的偏回归系数为0.124,差异有统计学意义(p0.05)。营养支持总热量的偏回归系数为0.520,差异有统计学意义(p0.05)。营养支持非蛋白质热量的偏回归系数为-0.459,差异有统计学意义(p0.05)。双歧杆菌的偏回归系数为-1.838,差异有统计学意义(p0.05)。熊去氧胆酸的偏回归系数为-2.325,差异有统计学意义(p0.05)。可看出营养支持方式、营养支持非蛋白质热量、双歧杆菌、UDCA与发生PNALD呈负相关,营养支持时间、营养支持总热量与PNALD的发生呈正相关。接受TPN患者比接受PN联合EN患者更易发生PNALD;营养支持总热量越高、非蛋白质热量越高,越易发生PNALD;营养支持时间越长,PNALD发生的可能性相应升高;应用双歧杆菌患者及应用UDCA患者均比不应用这两种药物患者,发生PNALD的可能性降低。4.不同联合用药研究组PNALD的发生率及营养支持前后肝功能变化情况171例研究对象中,联合应用双歧杆菌39人,联合应用UDCA 27人,未联合应用双歧杆菌及UDCA 105人,遂将研究对象分为双歧杆菌组(n=39)、UDCA组(n=27)及对照组(n=105)。双歧杆菌组发生PNALD的有4例,发生率为10.26%(4/39),其中联合应用TPN的有1例,发生率为16.67%(1/6),联合应用PN联合EN的有3例,发生率为9.09%(3/33);UDCA组发生PNALD的有2例,发生率为10.26%(2/27),其中联合应用TPN的有2例,发生率为20%(2/10),联合应用PN联合EN的有0例,发生率为0.00%(0/17);对照组发生其中PNALD的有28例,发生率为26.67%(28/105),其中应用TPN的有13例,发生率为35.14%(13/37),应用PN联合EN的有15例,发生率为22.06%(15/68)。具体结果见表7及图2。双歧杆菌各组及UDCA各组PNALD的发生率均比对照组相应降低。双歧杆菌联合PN+EN及UDCA联合PN+EN发生PNALD的比例比对照组单纯TPN发生PNALD的比例均明显降低,差异有统计学意义(p0.05)。将营养支持前的肝功能指标分别减去营养支持后的肝功能指标,得到新的变量△ALB,△ALT,△AST,△AKP,△γ-GT,△DBIL,△TBIL,△TBA,正数代表降低,负数代表升高,绝对值越大代表变量越大。双歧杆菌组△AKP平均值为(1.97±20.99),与对照组之间差异有统计学意义(p0.05),Ay-GT平均值为(-3.56±14.39),但差异无统计学意义(p0.05)。UDCA组△AKP、△DBIL、△TBIL 平均值分别为(-0.48±42.85)、(3.35±3.21)、(3.35±4.45),与对照组之间各指标差异均有统计学意义(p0.05),Ay-GT平均值为(-11.70±39.28),但差异无统计学意义(p0.05)。具体结果见表8。结论1.不同营养支持方式对PNALD的发生率影响有差异,且接受TPN的患者比接受PN联合EN的患者更易发生PNALD。2.PNALD的发生与营养支持方式、营养支持时间、营养支持总热量、营养支持非蛋白质热量、联合药物有关。3.双歧杆菌能够减少菌群异位,保护肠屏障,可能通过减轻胆汁淤积,保护肝功能,降低PNALD的发生率。4.UDCA能减轻胆汁淤积,降低胆红素,保护肝脏功能,减少PNALD的发生。
[Abstract]:Background our country has entered an aging society, and the aging process is accelerating gradually. The results of the sixth census show that China's population of 65 years and above is nearly 120 million, accounting for 8.87% of the total population. Compared with 2000, the proportion of aged 65 and above has risen by 1.91 percentage points. More and more attention has been paid to the particularity and complexity of senile disease, which makes the related research more special. It is found that the elderly hospitalized patients are more likely to have malnutrition and related diseases, and nutritional support is an important means to solve the problems of malnutrition and related diseases, but the complications associated with it are also caused. Attention. Parenteral nutrition associated liver damage (parenteral nutrition associated liver disease, PNALD) is one of the most common serious complications of parenteral nutrition support (parenteral nutrition, PN). Its etiology is diverse, including gastrointestinal basic diseases, bile acid intestinal obstruction, sepsis and dysbacteria, but its pathogenesis remains to be advanced. In one step, the focus is on the prevention and treatment of lipid influence, intestinal injury and nutritional imbalance.PNALD. In view of its cause and possible pathogenesis, it mainly focuses on reducing the effect of lipid, regulating intestinal flora, protecting intestinal barrier, reducing sepsis, unobstructing bile drainage, etc. Bifidobacterium is the human intestinal tract positive. One of the dominant bacteria in the common flora has positive significance for protecting intestinal barrier, alleviated heterotopic flora and sepsis, and its protection of liver function is becoming more and more important. In the PNALD model, it is found that Bifidobacterium plays a beneficial role in the prevention and control of PNALD, but it is still lacking in the study of PNALD in adult and old people. Xiong Quyang Cholic acid (UDCA) can increase the secretion of bile acid, promote bile excretion, reduce bilirubin and have a significant effect on the cholestasis caused by long term PN, but the study in PNALD of adults and old people is still not much. 1. Index changes, analysis of the status of parenteral nutrition support in elderly hospitalized patients and PNALD incidence of.2. analysis related factors (age, sex, nutrition support mode, time, total heat energy, non protein heat energy, drugs) on the effect of PNALD, explore a more reasonable nutritional support program.3. to explore the nutritional support combined Bifidobacterium therapy for liver function The effect of energy and the incidence of PNALD, provide reference.4. for clinical medication, explore the effect of nutrition support combined with UDCA on liver function and the incidence of PNALD, and provide reference for clinical use. A retrospective analysis of 171 cases of parenteral nutrition support in the Department of geriatrics of Qilu Hospital of Shandong University from May 2012 to October 2016 Subjects: age above 65 years old, parenteral nutrition support more than 7d, at least before nutrition support, the liver function indexes each time, and no obvious abnormal liver function before nutritional support, and exclude other causes of liver damage. A total of 171 cases were collected and collected: collect and statistics the general situation of the research subjects, nutritional support, nutritional support before support. The liver function index (the nearest index of distance nutrition support time), the liver function index after nutritional support (the nearest index of distance to the end of distance nutrition support), Bifidobacterium or UDCA application.3. research and Design: (1) analyze the general situation and nutritional support of the research subjects and compare the occurrence of PNALD under different nutritional support. (2) the subjects were divided into PNALD and normal liver function group, and compared and analyzed the differences of age, sex, nutrition scheme and nutrition support time between different research groups, and discussed the influence of related factors on PNALD; (3) the subjects were divided into Bifidobacterium, UDCA and control group (no Bifidobacterium and UDCA), and the comparison and analysis of different research groups Before the nutritional support, the changes in the function of the liver function were compared, the incidence of PNALD was compared, and the statistical method of the efficacy of the drug on the prevention of PNALD was discussed. The statistical analysis and chart were made with Excel 2007, SPSS 21 and GraphPad Prism 5. The measurement data were expressed with the mean standard deviation (x + s), which conformed to the normal distribution data with variance points. The difference between the groups was compared with the t test, and the difference in the normal distribution data was compared with the non parameter test. The number and percentage of the count data were compared, and the difference between the groups was compared with the chi square test. The data with the number of less than 5 in each group were tested with the exact probability of Fisher's. The multivariate statistical analysis of the factors affecting PNALD and the use of Logis Tic multivariate regression analysis was tested. With alpha =0.05 as the test standard, P0.05 indicated that the difference was statistically significant. Results there were 171 elderly hospitalized patients with 1. basic data. The average age was (79.45 + 7.44) years old, including 114 males (66.67%), average age (80.06 + 7.36) years, and 57 (33.33%) women (33.33%). Age (78.23 + 7.51) years. There was no significant difference in age and gastrointestinal diseases in different sexes (P0.05). See table 1.2. parenteral nutrition support and PNALD occurrence in 171 subjects, 53 cases (30.99%) received complete parenteral nutrition (total parenteral nutrition, TPN) treatment, and average nutritional support time (15.47) The average total heat (20.72 + 4.63) kcal/kg/d and average non protein heat (16.20 + 4.42) kcal/kg/d, 118 cases (69.01%) treated with enteral nutrition (EN), average nutritional support time (14.86 + 5.46) days, average total heat (21.72 + 8.74) kcal/kg/d, average non protein heat (17.51 + 7.95) kcal/kg/, were found in the average total calorie (5.31) days. D. received nutritional support time for different nutritional support methods, average total heat and average non protein heat differences were not statistically significant (P0.05). There were 34 cases (19.88%) of PNALD in the 2.171 subjects of the table, 16 of TPN patients with PNALD (30.19%), 118 received PN combined with EN treatment. There were 18 cases of PNALD (15.25%), and the incidence of PNALD in patients receiving different nutritional support was statistically significant (P0.05). The analysis of influencing factors of table 3.3.PNALD were divided into PNALD group (n=34) and normal liver function group (n=137). The basic situation of the two groups before treatment and the liver function index were found in group 4. two subjects There were no statistical differences in age, sex, and gastrointestinal disease (P0.05), and liver function indexes were in normal range. The two groups of subjects were nutritional support, nutritional support time, nutritional support total calorie, nutritional support for non protein heat, and the difference in drug difference were statistically significant (P0.05). See table 5. the effects of the above statistical differences The two element logistics regression analysis was carried out. The results showed that the partial regression coefficient of nutritional support was -0.967, and the difference was statistically significant (P0.05). The partial regression coefficient of nutritional support time was 0.124, the difference was statistically significant (P0.05). The partial regression coefficient of nutritional support total heat was 0.520, the difference was statistically significant (P0.05). The partial regression coefficient of non protein heat was -0.459, and the difference was statistically significant (P0.05). The partial regression coefficient of Bifidobacterium was -1.838, and the difference was statistically significant (P0.05). The partial regression coefficient of ursodeoxycholic acid was -2.325, and the difference was statistically significant (P0.05). CA has a negative correlation with the occurrence of PNALD, nutritional support time, the total calorie of nutritional support is positively correlated with the occurrence of PNALD. The patients receiving TPN are more likely to have PNALD than the PN combined with EN; the higher the total calorie, the higher the non protein calories, the more likely to occur PNALD; the longer the time of nutritional support, the higher the possibility of PNALD, and the application of double. Patients with SOD and UDCA were compared with those who did not use these two drugs. The possibility of PNALD was less likely to reduce the incidence of PNALD and the changes of liver function before and after nutritional support in the study group of.4.. The combined application of bifidobacteria 39 people combined with UDCA 27, and no joint application of Bifidobacterium and UDCA. 105 people, the subjects were divided into Bifidobacterium group (n=39), group UDCA (n=27) and control group (n=105). There were 4 cases of PNALD in Bifidobacterium group, the incidence rate was 10.26% (4/39), of which 1 cases were combined with TPN, the incidence rate was 16.67% (1/6), 3 cases combined PN combined EN, 9.09% (3/33), and 2 cases occurring in UDCA group, incidence rate. For 10.26% (2/27), there were 2 cases of combined use of TPN with 20% (2/10) and 0 cases combined with PN combined with EN (0% (0/17)), and 28 cases of PNALD in the control group were 26.67% (28/105), of which 13 were used in TPN, the incidence was 35.14% (13/37), 15 cases were used PN joint EN, the incidence of 22.06%. The specific results showed that the incidence of PNALD in each group of bifidobacteria and UDCA in all groups and UDCA groups was lower than that of the control group. The proportion of PNALD with PN+EN and UDCA combined with PN+EN in combination with Bifidobacterium and UDCA was significantly lower than that in the control group, and the difference was statistically significant (P0.05). The liver function indexes before nutritional support were reduced respectively. The indexes of liver function after degrading nutrition support, the new variable Delta ALB, Delta ALT, Delta AST, Delta AKP, Delta -GT, Delta DBIL, Delta TBIL, Delta TBA, the positive number represents a decrease, the negative number is higher, the greater the absolute value is, the higher the mean value is (1.97 + 20.99), and the difference between the control group and the control group is statistically significant (P0.05) and Ay-GT average. (-3.56 + 14.39), but the difference was not statistically significant (P0.05).UDCA group Delta AKP, Delta DBIL, Delta TBIL average value (-0.48 + 42.85), (3.35 + 3.21), (3.35 + 4.45), and the difference between the indexes of the control group was statistically significant (P0.05), Ay-GT mean (-11.70 + 39.28), but the difference was not statistically significant (P0.05). Specific results see table 8. conclusion 1. 1 Different nutritional support methods have different effects on the incidence of PNALD, and patients receiving TPN are more likely to have PNALD.2.PNALD occurrence and nutritional support, nutritional support time, nutritional support total calorie, nutritional support for non protein calorie, and combined drug related bifidobacteria to reduce ectopic bacterial heterotopia in patients with PN combined with EN. Protective intestinal barrier may reduce cholestasis by reducing cholestasis, protecting liver function and reducing the incidence of PNALD,.4.UDCA can reduce cholestasis, reduce bilirubin, protect liver function, and reduce the occurrence of PNALD.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575

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