發(fā)布時(shí)間：2018-04-27 15:01

  本文選題：老年住院患者 + 腸外營養(yǎng)相關(guān)性肝損害��； 參考：《山東大學(xué)》2017年碩士論文

【摘要】：研究背景我國已步入老齡化社會(huì),且老齡化進(jìn)程在逐步加快。第六次人口普查結(jié)果顯示,我國65歲及以上人口近1.2億,占總?cè)丝诘?.87%,同2000年相比,65歲及以上老齡人口的比重上升了 1.91個(gè)百分點(diǎn)。隨著老齡人口的不斷增加,老年住院患者得到越來越多的關(guān)注,且由于老年疾病的特殊性和復(fù)雜性,使得其相關(guān)研究更具特殊意義。研究發(fā)現(xiàn),老年住院患者更容易發(fā)生營養(yǎng)不良及相關(guān)疾病,而營養(yǎng)支持是解決營養(yǎng)不良及其相關(guān)疾病問題的重要手段,但其伴隨的并發(fā)癥亦引起重視。腸外營養(yǎng)相關(guān)性肝損害(parenteral nutrition associated liver disease,PNALD)是腸外營養(yǎng)支持(parenteral nutrition,PN)常見的嚴(yán)重并發(fā)癥之一。其病因多樣,包括胃腸道基礎(chǔ)性疾病、膽汁酸腸肝循環(huán)障礙、膿毒血癥、菌群失調(diào)等,但其發(fā)病機(jī)制尚待進(jìn)一步研究,目前比較集中的觀點(diǎn)是脂質(zhì)影響、腸道損傷和營養(yǎng)失衡。PNALD的預(yù)防治療,針對(duì)其病因及可能的發(fā)病機(jī)制,主要圍繞減輕脂質(zhì)影響、調(diào)節(jié)腸道菌群、保護(hù)腸道屏障、減少膿毒血癥、通暢膽汁引流等方面進(jìn)行。雙歧桿菌是人體腸道正常菌群中的優(yōu)勢菌種之一,對(duì)保護(hù)腸屏障、減輕菌群異位及膿毒血癥有積極意義,其對(duì)肝功能的保護(hù)也日益得到重視。有研究在PNALD模型中發(fā)現(xiàn)雙歧桿菌在防治PNALD中發(fā)揮有益的作用,但其在成人及老年人PNALD中尚缺乏相關(guān)研究。熊去氧膽酸(UDCA)能夠增加膽汁酸的分泌,促進(jìn)膽汁排出,降低膽紅素,對(duì)于新生兒由于長期PN引起的膽汁淤積有顯著療效,但其在成人及老年人PNALD中的研究尚不多見。研究目的1.調(diào)查老年住院患者腸外營養(yǎng)支持情況,評(píng)估營養(yǎng)支持前后肝功能指標(biāo)變化情況,分析老年住院患者腸外營養(yǎng)支持現(xiàn)狀及PNALD發(fā)生情況。2.分析相關(guān)影響因素(年齡、性別、營養(yǎng)支持方式、時(shí)間、總熱能、非蛋白質(zhì)熱能、藥物)對(duì)PNALD的影響,探尋更合理的營養(yǎng)支持方案。3.探討營養(yǎng)支持聯(lián)合雙歧桿菌治療對(duì)肝功能的影響及PNALD發(fā)生率,為臨床用藥提供參考。4.探討營養(yǎng)支持聯(lián)合UDCA治療對(duì)肝功能的影響及PNALD發(fā)生率,為臨床用藥提供參考。研究方法回顧性分析2012年5月至2016年10月山東大學(xué)齊魯醫(yī)院老年病科171例腸外營養(yǎng)支持患者歸檔病歷。1.研究對(duì)象:年齡≥65歲,腸外營養(yǎng)支持≥7d,至少有營養(yǎng)支持前、后的肝功能指標(biāo)各一次,且營養(yǎng)支持前的肝功能指標(biāo)無明顯異常,并排除肝損害的其他病因。共納入171例。2.資料收集:收集并統(tǒng)計(jì)研究對(duì)象的一般情況、營養(yǎng)支持情況、營養(yǎng)支持前的肝功能指標(biāo)(為距離營養(yǎng)支持開始時(shí)間最近指標(biāo))、營養(yǎng)支持后的肝功能指標(biāo)(為距離營養(yǎng)支持結(jié)束時(shí)間最近指標(biāo))、雙歧桿菌或UDCA應(yīng)用情況。3.研究設(shè)計(jì):(1)分析研究對(duì)象一般情況及營養(yǎng)支持情況,比較不同營養(yǎng)支持情況下PNALD的發(fā)生情況;(2)將研究對(duì)象分為PNALD和肝功能正常組,對(duì)比分析不同研究組之間年齡、性別、營養(yǎng)方案、營養(yǎng)支持時(shí)間等的差異,探討相關(guān)因素對(duì)PNALD的影響;(3)將研究對(duì)象分為雙歧桿菌組、UDCA組和對(duì)照組(未聯(lián)合雙歧桿菌及UDCA),對(duì)比分析不同研究組之間營養(yǎng)支持前、后肝功能指標(biāo)變化情況,比較PNALD的發(fā)生率,探討藥物對(duì)PNALD預(yù)防的有效性。4.統(tǒng)計(jì)學(xué)方法:采用Excel 2007、SPSS 21.0及GraphPad Prism 5進(jìn)行統(tǒng)計(jì)學(xué)分析及圖表繪制。計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,符合正態(tài)分布資料用方差分析和t檢驗(yàn)比較組間差異,不符合正態(tài)分布資料用非參數(shù)檢驗(yàn)比較組間差異。計(jì)數(shù)資料用例數(shù)和百分比表示,用卡方檢驗(yàn)分析比較組間差異;各組例數(shù)小于5的資料的用Fisher's精確概率進(jìn)行檢驗(yàn)。對(duì)PNALD影響因素的多元統(tǒng)計(jì)學(xué)分析,使用logistic多元回歸分析進(jìn)行檢驗(yàn)。以α=0.05為檢驗(yàn)標(biāo)準(zhǔn),P0.05表示差異有統(tǒng)計(jì)學(xué)意義。結(jié)果1.研究對(duì)象基本資料共有171例老年住院患者納入本次研究,平均年齡為(79.45±7.44)歲,其中包括男性114例(66.67%),平均年齡(80.06±7.36)歲,女性57例(33.33%),平均年齡(78.23±7.51)歲。不同性別患者在年齡、胃腸道疾病的比較上,差異無統(tǒng)計(jì)學(xué)意義(p0.05),見表1。2.腸外營養(yǎng)支持情況及PNALD發(fā)生情況171例研究對(duì)象中有53例(30.99%)接受了完全腸外營養(yǎng)(total parenteral nutrition,TPN)治療,平均營養(yǎng)支持時(shí)間(15.47±5.31)天,平均總熱量(20.72±4.63)kcal/kg/d,平均非蛋白質(zhì)熱量(16.20±4.42)kcal/kg/d;接受腸外聯(lián)合腸內(nèi)營養(yǎng)(enteral nutrition,EN)治療的有118例(69.01%),平均營養(yǎng)支持時(shí)間(14.86±5.46)天,平均總熱量(21.72±8.74)kcal/kg/d,平均非蛋白質(zhì)熱量(17.51±7.95)kcal/kg/d。接受不同營養(yǎng)支持方式治療患者的營養(yǎng)支持時(shí)間、平均總熱量及平均非蛋白質(zhì)熱量差異均無統(tǒng)計(jì)學(xué)意義(p0.05),見表2。171例研究對(duì)象中發(fā)生PNALD的有34例(19.88%),53例接受TPN患者中發(fā)生PNALD的有16例(30.19%),118例接受PN聯(lián)合EN治療患者中發(fā)生PNALD的有18例(15.25%),接受不同營養(yǎng)支持方式治療患者PNALD的發(fā)生率差異有統(tǒng)計(jì)學(xué)意義(p0.05),見表 3。3.PNALD影響因素分析將研究對(duì)象分為PNALD組(n=34)和肝功能正常組(n=137)。兩組患者治療前基本情況及肝功能指標(biāo)見表4。兩組研究對(duì)象之間年齡、性別、胃腸道疾病均無統(tǒng)計(jì)學(xué)差異(p0.05),肝功能指標(biāo)均在正常范圍。兩組研究對(duì)象之間營養(yǎng)支持方式、營養(yǎng)支持時(shí)間、營養(yǎng)支持總熱量、營養(yǎng)支持非蛋白質(zhì)熱量、藥物差異均有統(tǒng)計(jì)學(xué)意義(p0.05),見表5。將上述有統(tǒng)計(jì)學(xué)差異的影響因素進(jìn)行二元logistics回歸分析,結(jié)果見表6。營養(yǎng)支持方式的偏回歸系數(shù)為-0.967,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。營養(yǎng)支持時(shí)間的偏回歸系數(shù)為0.124,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。營養(yǎng)支持總熱量的偏回歸系數(shù)為0.520,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。營養(yǎng)支持非蛋白質(zhì)熱量的偏回歸系數(shù)為-0.459,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。雙歧桿菌的偏回歸系數(shù)為-1.838,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。熊去氧膽酸的偏回歸系數(shù)為-2.325,差異有統(tǒng)計(jì)學(xué)意義(p0.05)�？煽闯鰻I養(yǎng)支持方式、營養(yǎng)支持非蛋白質(zhì)熱量、雙歧桿菌、UDCA與發(fā)生PNALD呈負(fù)相關(guān),營養(yǎng)支持時(shí)間、營養(yǎng)支持總熱量與PNALD的發(fā)生呈正相關(guān)。接受TPN患者比接受PN聯(lián)合EN患者更易發(fā)生PNALD;營養(yǎng)支持總熱量越高、非蛋白質(zhì)熱量越高,越易發(fā)生PNALD;營養(yǎng)支持時(shí)間越長,PNALD發(fā)生的可能性相應(yīng)升高;應(yīng)用雙歧桿菌患者及應(yīng)用UDCA患者均比不應(yīng)用這兩種藥物患者,發(fā)生PNALD的可能性降低。4.不同聯(lián)合用藥研究組PNALD的發(fā)生率及營養(yǎng)支持前后肝功能變化情況171例研究對(duì)象中,聯(lián)合應(yīng)用雙歧桿菌39人,聯(lián)合應(yīng)用UDCA 27人,未聯(lián)合應(yīng)用雙歧桿菌及UDCA 105人,遂將研究對(duì)象分為雙歧桿菌組(n=39)、UDCA組(n=27)及對(duì)照組(n=105)。雙歧桿菌組發(fā)生PNALD的有4例,發(fā)生率為10.26%(4/39),其中聯(lián)合應(yīng)用TPN的有1例,發(fā)生率為16.67%(1/6),聯(lián)合應(yīng)用PN聯(lián)合EN的有3例,發(fā)生率為9.09%(3/33);UDCA組發(fā)生PNALD的有2例,發(fā)生率為10.26%(2/27),其中聯(lián)合應(yīng)用TPN的有2例,發(fā)生率為20%(2/10),聯(lián)合應(yīng)用PN聯(lián)合EN的有0例,發(fā)生率為0.00%(0/17);對(duì)照組發(fā)生其中PNALD的有28例,發(fā)生率為26.67%(28/105),其中應(yīng)用TPN的有13例,發(fā)生率為35.14%(13/37),應(yīng)用PN聯(lián)合EN的有15例,發(fā)生率為22.06%(15/68)。具體結(jié)果見表7及圖2。雙歧桿菌各組及UDCA各組PNALD的發(fā)生率均比對(duì)照組相應(yīng)降低。雙歧桿菌聯(lián)合PN+EN及UDCA聯(lián)合PN+EN發(fā)生PNALD的比例比對(duì)照組單純TPN發(fā)生PNALD的比例均明顯降低,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。將營養(yǎng)支持前的肝功能指標(biāo)分別減去營養(yǎng)支持后的肝功能指標(biāo),得到新的變量△ALB,△ALT,△AST,△AKP,△γ-GT,△DBIL,△TBIL,△TBA,正數(shù)代表降低,負(fù)數(shù)代表升高,絕對(duì)值越大代表變量越大。雙歧桿菌組△AKP平均值為(1.97±20.99),與對(duì)照組之間差異有統(tǒng)計(jì)學(xué)意義(p0.05),Ay-GT平均值為(-3.56±14.39),但差異無統(tǒng)計(jì)學(xué)意義(p0.05)。UDCA組△AKP、△DBIL、△TBIL 平均值分別為(-0.48±42.85)、(3.35±3.21)、(3.35±4.45),與對(duì)照組之間各指標(biāo)差異均有統(tǒng)計(jì)學(xué)意義(p0.05),Ay-GT平均值為(-11.70±39.28),但差異無統(tǒng)計(jì)學(xué)意義(p0.05)。具體結(jié)果見表8。結(jié)論1.不同營養(yǎng)支持方式對(duì)PNALD的發(fā)生率影響有差異,且接受TPN的患者比接受PN聯(lián)合EN的患者更易發(fā)生PNALD。2.PNALD的發(fā)生與營養(yǎng)支持方式、營養(yǎng)支持時(shí)間、營養(yǎng)支持總熱量、營養(yǎng)支持非蛋白質(zhì)熱量、聯(lián)合藥物有關(guān)。3.雙歧桿菌能夠減少菌群異位,保護(hù)腸屏障,可能通過減輕膽汁淤積,保護(hù)肝功能,降低PNALD的發(fā)生率。4.UDCA能減輕膽汁淤積,降低膽紅素,保護(hù)肝臟功能,減少PNALD的發(fā)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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575

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