益富新普派-保肠旺(NU-PEP HN)临床使用报告.doc

益富新普派-保腸旺(NU-PEP HN)臨床使用報告前言:一. 元素飲食使用原因: 元素飲食於臨床上應用已有多年，主要對象有兩類，第一類是先前已使用靜脈營養(parenteral Nutrition)，一段時間內準備轉換至腸道營養(Enteral Nutrition)前，給予元素飲食測試腸道功能的復甦能力。第二類對象，因疾病或手術造成永久性腸道消化吸收功能不全者，需要長期使用元素飲食，以供給足夠的營養，例如Short Bowel Syndrome(短腸症)，Inflammatory Bowel Disease(發炎性腸病變)，Cystic Fibrosis(囊腫纖維變性),Ulcerative Colitis(潰瘍性結腸炎,Chronic Pancreatitis(慢性胰臟炎)，Acute Pancreatitis(急性胰臟炎),Radiation Enteritis(輻射性腸炎)等。 目前市售元素飲食的成分以葡萄糖、胺基酸為主，只含少量脂肪酸，無法提供足夠的蛋白質、脂肪及熱量，對於需要較長期使用元素飲食為主要營養來源的病患之營養狀況不易確保。新普派-保腸旺(Nu-PEP HN)含高蛋白質(20%熱量)，且為l00%的水解乳清胜月太 (peptide)，較游離胺基酸(Free Amino Acid)更易被腸道吸收利用，同時提高脂肪含量(15%熱量)，其中50%為不需經過膽汁乳糜化及脂肪酸消化，就可直接經血液吸收的中鏈脂肪酸(medium chain triglyceride)，並可提供足夠的必需脂肪酸，至於每日所需的必須維生素、礦物質的含量，每15OOkcal Nu-PEP HN可達到100%每日營養建議需要量(RDNA)，彌補目前市售元素飲食的缺點，應是較好的選擇，適宜病患短期與長期使用。二.使用元素配方考慮的因素1.滲透壓：配方產品的滲透壓在400mOsm/KgH2O以下，一般可以立即使用，可減少高滲透壓導致的腹瀉。(（NU-PEP）保腸旺395mOsm/公斤符合此標準)。2.熱量：供應濃度為每1毫升含1卡(保腸旺符合此標準)。3.蛋白質：對消化不良、吸收不良，需要容易消化形式蛋白質者，水解乳清胜月太 (peptide)是良好來源，在各方面上短鏈胜月太 比游離胺基酸更容易吸收且被接受(保腸旺符合此原則)。4.脂質：MCT於缺乏胰脂解酶 與膽鹽時仍可以被消化分解成小分子，直接吸收進入肝門靜脈。(保腸旺符合此原則)，含有中鏈三酸甘油酯（MCT），適用於消化吸收不良患者。5.醣類:麥芽糊精，易水解小分子後被吸收(保腸旺符合此原則)。6.維生素和礦物質：強化維生素和礦物質以符合飲食建議量（RDA）(保腸旺符合此標準)。三.由靜脈營養到經腸道或經口配方需注意事項: 考量患者對於配方味道的接受程度及灌食速率。建議剛開始使用簡單液狀食物及滲透壓不超過400mOsm/kg的配方。鼓勵食用營養密度高的物質以建立足夠量的經口飲食為止，如乳清水解配方(保腸旺符合此原則)，約3到4天可以終止靜脈營養。四.有關蛋白質的營養消化生理文獻參考:Board Review Series Physiology,Linda S.Costanzo:200-202,1995 Protein Can be absorbed as amino acids, dipeptides, and tripeptides (incontrast to carbohydrates, which can only be absorbed as monosaccharides)1. Digestion of proteins a. Endopeptidases -degrade proteins by hydrolyzing interior peptide bonds. b. Exopeptidases -hydrolyze one amino acid at a time from C terminal of protein. and peptides. c. Pepsin -is secreted as pepsinogen by the chief cells of the stomach. -is not essential for protein digestion。 -Pepsinogen is activated to pepsin by gastric H. d. Pancreatic proteases -are secreted in an inactive form and are activated by brush border enzymes.-For example, trypsinogen is secreted by the pancreas and is activated to trypsin by enterokinase in the small intestine.2. Absorption of protein (如圖1.) Machanism of absorption of a.a. , dipeptide, and tripeptides by intestinal epithelial cells. a.Absorption of free amino acids-There is Na+ -dependent secondary active transport of amino acids in the luminal membrane ,analogous to the transporter for glucose and galactose.-The amino acids are subsequently transported from cell to blood by facilitated diffusion and simple diffusion. -There are four separate carriers fur neutral, acidic, basic, and imino amino acid, respectively. b. Absorption as dipeptide and tripeptides -*is faster than absorption of free amino acids.-There is Na*-dependent secondary active transport for dipeptides and tripeptides in the luminal membrane. -Once the dipeptides and tripeptides have been transported into the intestinal cells, cytoplasmic peptidases hydrolyze them to amino acids. They are then transported from cell to blood by facilitated and simple diffusion.Lumen of intestine Epithelial cell of small intestine Blood 圖1 Amino acids Amino acids Na+ peptidases Dipeptide and tripeptides Na+ Na+ K+材料與方法：一.材料: 新普派-保腸旺，營養成分分析如下表:營養成分：(每100公克)熱量400大卡生物素53微克蛋白質20公克膽鹼26.7毫克脂肪6.9公克牛磺酸26.7毫克 中鏈脂肪3.4公克L-肉酸40毫克碳水化合物65.1公克鈉411毫克維生素A1337 I.U.鉀428毫克危收素D107 I.U.氯444毫克維生素E16 I.U.鈣267毫克維生素K19微克磷267毫克維生素C32毫克鎂107毫克維生素B1800微克鐵4.8毫克維生素B2900微克碘40微克維生素B6800微克銅0.5毫克維生素B122.4微克鋅5.3毫克菸鹼酸8000微克錳1.3毫克葉酸161微克硒21微克泛酸4021微克鉬24微克滲透壓395mOsm/KgH2O鉻21微克二.方法：1.保腸旺（NU-PEP）營養支持流程.l*.Subject : 2000/42000/10(1) undergoing gastrointestinal surgical NST consulted. Using TPN transition TEN (2) pancreatitis need NPO3days and uses TPN. l* Method : Feeding D5w 25ml/hr (11.5day)- (Nu-pep) full strength element diet 25ml/hr .(2day) progressed to optimal goal by 5days are 6585ml/hr. * Observation: (1) biochemical data, (2) feeding complication: GI symptoms, (3) complication, wound infection, pneumonia, sepsis. (4) clinical outcome .* If moderate to severe GI symptoms: feeding was discontinued for 6 to 12 hrs then started again at 25ml/hr.2.為觀察新普派-保腸旺(Nu-PEP HN)在臨床應用上對病患營養狀態及腸道吸收的耐受情況，以振興醫院外科病患20位為對象，其性別、年齡、診斷等基本資料如表一。*試驗期間為5+3天。*營養供給的原則主要為:(1) 以Harris-Benedict公式估算病患熱量需要量。(2) 採腸道營養連續灌食方式，其灌食途徑可由鼻胃管(Nasogastric)，或鼻十二指腸管(Nasoduodenal)，或造口手術(-ostomy)。(3) 在尚未以腸道灌食達至建議量之前，可以週邊靜脈營養輸入(PPN)輔助達到建議量。*Nu-PEP灌食的步驟:(1) 開始以25c.c/hr full strength(lkcal/1cc)24小時連續管灌餵食，並密切觀察腸胃耐性情況(記錄腹瀉、腹脹等的發生)。(2) 若耐受情況良好，則在第二天增加管灌量為355Oc.c./hr。(3) 若耐受情況仍是良好，則第三天繼續增至5075c.c./hr。(4) 而第46天可開始漸漸轉換元素飲食為一般完全配方(polymeric formula)。若耐受情況不佳(如腹瀉、腹脹)，則調整灌食量(可重覆)，直到耐受情形正常，再增加灌食量。(5)每日巡查病患，依腸道耐受情況而酌量調整灌食量。(6)另外分別在試驗開始(第一天pre-test)及試驗結束(第十天-post-test)各抽一次血，檢測白蛋白(albumin)，前白蛋白(pre-albumin)及運鐵素(Transferrin)，腎功能與肝功能，以及每日腸道耐受性(嘔吐、腹脹、腹瀉、便秘)，做為觀察營養狀態變化及接受性的指標。結果: 20位試驗對象，皆為腸胃道大手術的患者，其實際營養供給進行步驟極個別性(如表二.）。其腸道耐受情形觀察結果， 只有1人出現腹瀉現象，腹脹天數佔使用天數的20%、嘔吐佔總使用天數的8，其餘患者耐受情況良好(如表三.)。血液生化值檢測結果，都可維持術前的營養狀況(如表四.)，肝功能、腎功能使用後都在正常的範圍(如表五)，生命癥象都在可接受的範圍(如表六.)。表一：受試者基本資料受試性別年齡身高體重診斷1F7715154Intestinal obstruction,acute cholecystitis 2M7316870S/p aorta reconstruction, r/o ileus.3F 6515153Pancreatitis, cholelithiasis CBD stone4M6016554Gastric Ca5M5916883Intestinal obstruction6F8715553UGI bleeding,PPU 7M6316463Gastric Ca8F6048Pancreatitis, cbd stone,cholecystectomy9M8515850Intestinal obstruction,intestinal resection10M7816264Gastric Ca11F4215034Gastric Ca12M3548Colon perforation13F7916850Ppu 14M4316554Acute pancreatitis, s/pancreatectomy15F6214646Intestinal bleeding,intestinal supture16M5216268Gastric Ca, subtotal gastrectomy17M7615747Pancreatic tumor,pancreatic head resection18F8850Cholectomy ,ileus19M6416064Acute pancreatitis, cholecystectomy20F7316476Gastric Ca,subtotal gastrectomy表二：受試者營養供給過程受試者營養建議量/天營養處方供給進展使用天數（轉換一般配方）佔營養建議量11620TPN +D5w -TPN+ nupep standard formula 553.121872TPN +D5w -TPN+ nupep standard formula549.731606TPN +D5w -TPN+ nupep standard formula 5106.241741TPN +D5w -TPN+ nupep standard formula568.952266TPN +D5w -TPN+ nupep standard formula 334.461590TPN +D5w -TPN+ nupep standard formula669.971843TPN +D5w -TPN+ nupep standard formula 443.181440TPN +D5w -TPN+ nupep standard formula561.191387TPN +D5w -TPN+ nupep standard formula 592.3101681TPN +D5w -TPN+ nupep standard formula463.1111496TPN +D5w -TPN+ nupep standard formula 558.0121440TPN +D5w -TPN+ nupep standard formula581.9131500TPN +D5w -TPN+ nupep standard formula 1062.7141927TPN +D5w -TPN+ nupep standard formula468.3151503TPN +D5w -TPN+ nupep standard formula 582.2162054TPN +D5w -TPN+ nupep standard formula443.8171219TPN +D5w -TPN+ nupep standard formula 473.8181500TPN +D5w -TPN+ nupep standard formula586.7191887TPN +D5w -TPN+ nupep standard formula 337.6202280TPN +D5w -TPN+ nupep -standard formula539.5Mean+SD 1693+288564+10%表三：受試者腸道耐受性(發生天數/使用天數) 受試者使用天數腹瀉(day/T. day)腹脹(day/T. day)嘔吐(day/T. day)1503025010350104501153021661307400085033950111040011150001250111310040144000155000164000174000185010193000205000Total971/97(1%)21/97(21%)8/97(8%)表四：受試者血液生化質檢測結果(一)AlbTLCPrealbumintransferrin CholTGpreposPo-prPreposPo-prPreposPo-prpreposPo-prPrePosPo-prpreposPo-pr12.82.90.1141014100135142722.92.8-0.115601210-3509814143120105-1510288-1435.25.20135017804303230.6-1.41681983010810804440-443.83.80960960016.918.41.517118312119109-106060052.92.9011301130018.218.201261260172170-2133120-1362.83.10.311501350200126116-10130120-1073.13.10138014608029.523.5-614214311681680104104083.13.10174017400157150-78180-1932.8-0.213501150-20013.411-2.41201211.21381380749824103.13.40.31090109001616.20.2124104-2015116091091090114.33.8-0.5970180083018.417.3-1.1163163058259201124.24.20123012300238230-8121110-11132.52.1-0.431011988885471177262-10142.92.9059093034079.22.2176116-60859052032030152.93.30.41380770-61023.223.20217133-841281280249142-107163.83.8010101010027.620.2-7.4275238-3710181-201501500173.12.6-0.56307501201419514416824141140-172720182.82.6-0.2185030601210808006151-10193.23.201670180013011.311.30767609389-4202.42.4013501350014.614.70.113013449990-99490-4表四-1：受試者血液生化質檢測結果（一） 平均值AlbTLCPrealbuminTransferrin CholTGpreposPo-prPreposPo-prPreposPo-prpreposPo-prPrePosPo-prpreposPo-prMean3.243.2-0.041206135915318.6217.90-0.46158151.4-4.29126124-2.210610822SD0.690.703905157.435.8346.7737.5942415253表五：受試者血液生化質檢測結果（二）ASTALTBUNCr. KPreposPo-prPreposPo-prPrePosPo-prpreposPo-prprePosPo-pr13131024240353501103.93.9029180-1185148633614-221.51.3-0.23.73.5-0.23459752337137-2002217-50.91.10.24.44.70.34121207701313011044051616018180121200.80.803.63.606181802222071103.53.507222209465-2977010.7-0.34.44.408212107325-48191900.60.604.13.9-0.29284113496617121420.80.90.14.14-0.110347036294920252501.21.203301127270243915363600.50.503.73.701226260262603966271.92.40.54.43.5-0.91329290778912921120.40.50.13.33.80.51453530326331222200.80.804.44.401540444172034337-611.20.22.84.41.616282801029199900.90.90440179741-568051-29101000.80.7-0.12.94.41.5183921-185123-28131960.60.80.24.53.2-1.3193635-14325-18162150.71.10.43.94.40.5202222012120101000.60.603.23.20表五-1：受試者血液生化質檢測結果（二）平均值ASTALTBUNCr. KPreposPo-prPreposPo-prPrePosPo-prprePosPo-prprePosPo-prMean35.7536.70.9557.7948.74-8.619.7521.40.60.90.960.063.793.880.09SD22.2922.5672.1139.6811.8814.00.340.410.530.48表六：受試者使用期間 Vital sign 檢測結果（三）R.RBPHeart ratePrePosPrePosPrePos12223130/82 132/70657821818132/76116/70827632022120/80130/70988441920100/70118/80729852120130/70135/69708561423109/4590/43768171920148/66143/661159482019120/80124/80708892021120/80120/808496101818128/78110/7809888112020130/85122/767879121719145/82130/808582132014102/45111/56102156142023159/92129/8611090151823122/78104/70113112162018120/90130/807080171820145/86142/829085181717136/82133/698589192020130/80110/7094100201719118/69122/787882表六：受試者使用期間 Vital sign 檢測結果（三）平均值R.RBPHeart ratePrePosPrePosPrePosMean18.819.9127/76123/738791SD1.82.315/1313/101517 表七：受試者住院其間，Clinical outcome: 受試者Icu daysAdm.days1142626303621441857666177725869295201051211423128791369811411331511181631117526188321991920519表七-1：受試者住院其間，Clinical outcome : 平均值受試者Icu daysMortality住院天數mean10 day20%30 day討論：l.NU-PEP HN應用在TPN transfer to TEN頗為順利，從腸道的耐受性觀察，各種副作用(如腹瀉、腹脹、嘔吐等)皆少發生，使病患順利漸漸減少靜脈營養，而逐步轉為腸道營養供給，使腸道功能得到良好的復甦。2.研究指出重症患者其手術後與住院期間，會因處於壓力之下而處於較高的代謝分解期，以致常有嚴重營養不良狀態，若沒有適當的營養支持，會加劇其營養不良狀態，從試驗前後血液生化檢測值的變化來看，Nu-Pep的營養介入，均能使受試者維持其營養狀況。本研究結果，由受試者血清白蛋白、前白蛋白、運鐵素、三酸甘油酯、膽固醇的數值分析，可顯示適當的靜脈與腸道營養支持，可以使重症病患維持營養狀況，避免營養不良惡化。文獻回顧:(1) 主題:enteral vs. TPN 方法:Meta-Analysis Consisting of 230 patients % of patients with postoperative septic結果:16% of TEN patients suffered septic complication as compared with 35% of patients in the TPN group (P0.05) Ref:Linda SC.physiology.1995;200-202.(2) 主題: Nutritional response of patients in an intensive care unit to an elemental formula vs standard formula 方法:pts have malabsorption , received tube feeding ,hepatic disease ,renaldisease ,hypoalbumin . determined :albumin ,prealbumin,urea nitrogen. 結果:no evidence was found to support a benefit from an elemental formula . Ref: J Eileen D, Charles JF,Randall WS. J Am Diet Assoc.1998;98:335-336. (3) 主題:Efficiency of enteral nitrogen support in surgical patients:small peptides v non-degrades proteins. 方法abdominal surgery ,laparotomy.n12 .determined protein meta. 結果:pts in ICU after abdominal surgery enteral support containing small peptides is more effective than an equivalent diet containing whole proteins in restoring plasma amino acid and protein levels. Ref: F Ziegler, JM Ollivier, L Cynober.Gut.1990;31:1277-1283.(4)主題:Comparison of amino acid v peptide based enteral diets in active Crohns disease: clinical and nutritional outcome. 方法:40 pts with Crohns disease diagnosed by established radiological or endoscope findings nutritional assessment:albumin,transferrin,phospholipid,body total body nitrogen 結果:The study shows that peptide based high fat diets for achieving clinical remission in active Crohns disease. Improved total body protein stores but essential fatty acid depletion may be an important indicator of a sustained remission. Ref:Droyall,KN Jeejeebhoy,JP Baker. Gut.1994;35:783-787. (5)主題:Controlled trial of oligopeptide versus amino acid diet in treatment of active Crohns disease. 結果:The two diets were equally effective .1.Patients who resp