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1、如何合理实施临床营养支持How to Implement Rational Clinical Nutrition Therapy,吴国豪复旦大学附属中山医院普外科 复旦大学普通外科研究所,为什么需要营养支持?那些病人需要营养支持?,如何进行合理的营养支持？,第一部分,Prevalence of malnutritionThe German hospital malnutrition study,Matthias Pirlich，Clinical Nutrition(2006)25,563572,癌性恶病质的发生率,N A Stephens;MEDICINE 2007;36:(2):78-81,
2、Malnutrition is common in cancer patients,Malnutrition occurs in 30-87%of cancer patients Shills ME;et al:Cancer Res 1977;37:2366Nixon DW et al:Am J Med1980;68:683Tchekmedyian NS et al:Oncology 1995;9:79 Andreyev et al:Eur J Cancer 1998;34:503Monitto CL et al:Am J Physiol 2001;281:E289Stephens NA et
3、 al:Medicine 2007;36:(2):78-81,营养不良的危害,免疫机能下降,脏器功能异常,预后不良,Cumulative Mortality:Protein-Energy Malnutrition,Cederholm et al,Am J Med 1995.,Mortality%,Months after admission,P0.01,Malnutrition Is Associated with Increased Complications,Numerous studies have demonstrated complications of malnourished p
4、atients to be 2-20 times greater than those of well nourished patients.,Buzby et al,Am J Surgical 1980.Hickman et al,JPEN 1980.Klidjian et al,JPEN 1982.,Malnutrition Is Associated with Increased Complications,42%of patients with severe malnutrition experience major complications9%of patients with mo
5、derate malnutrition experience major complicationsSeverely malnourished patients are four times as likely to have post-operative complications as well-nourished patients,Detsky et al,JPEN 1987.Detsky et al,JAMA 1994.,Clinical Outcomes of malnutrition,Tewari N，et al:Lung Cancer(2007)57,389394,Clinica
6、l Outcomes of malnutrition,Pirlich M，Clinical Nutrition(2006)25,563572,Clinical Outcomes of malnutrition,p 0.001;,Schiesser M et al:Clinical Nutrition 2008;27:565-570,608 patients admitted for elective gastrointestinalsurgery.Nutritional risk was defined by NRS 2002 and correlated to the incidence o
7、f postoperative complications,Clinical Outcomes of malnutrition,NRS 2002,p 0.001;,Schiesser M et al:Clinical Nutrition 2008;27:565-570,P0.001,PJ Ross；British Journal of Cancer(2004)90,1905 1911,Clinical Outcomes of malnutrition,Bachmann J，J Gastrointest Surg(2008)12:11931201,作用与目标:调整病人的代谢改变及内 稳态失衡,改
8、善营养状态与免疫机能 降低医院获得性感染发生率缩短住ICU时间最终改善病死率,营养支持在疾病治疗中的作用,营养支持对营养状态的影响,*P=0.04,Klein S,JPEN 1997,21:133,Nutritional Therapy Affects Outcomes,Bragan Arch Surg 2002;137:174,*P=0.02,Nutritional Therapy Affects Outcomes,Bragan Arch Surg 2002;137:174,*P=0.001,Nutritional Therapy Affects Outcomes,Neumayer LA J
9、 Surg Res 2001;95:757,Nutritional Therapy Affects Outcomes,Neumayer LA J Surg Res 2001;95:757,*P=0.0001,Nutritional Therapy Affects Outcomes,Bozzetti F JPEN 2000;24:4-14,*P=0.03,*P=0.02,Nutritional Therapy Affects Outcomes,Fan ST et al:N Engl J Med 1994;331:1547,*P=0.02,Nutritional Therapy Affects O
10、utcomes,Fan ST et al:N Engl J Med 1994;331:1547,*P=0.01,Nutritional Therapy Affects Outcomes,Fan ST et al:N Engl J Med 1994;331:1547,*P=0.004,问题二:那些病人需要营养支持?,Which patients should we feed?,which patients can safely be left to resume feeding themselves?14 days starvation-dangerous depletion of lean b
11、ody massmortality rises in ICU patients with a second week of severe under-feeding5 days without feed increases infections but not mortalityone view is therefore that 5-7 days is the limit,Which patients should we feed?,all malnourished patientsall patients who are unlikely to regain normal oral int
12、ake within either 2 or 5-7 days depending on your viewone meta-analysis suggests reduced infections if patients are fed within 48 hoursone meta-analysis of early TPN versus delayed EN found reduced mortality with early feeding,外科病人的营养支持,围手术期营养支持短肠综合征炎性肠道疾病肠外瘘重症胰腺炎危重病人器官移植,围手术期营养支持指征,目前认为:营养状况良好病人可耐受
13、一般手术创伤,10天内无营养支持不会产生副作用严重营养不良患者;中等程度营养不良而需接受重大手术患者;手术后一周以上禁食者;手术前营养支持者;严重营养不良而手术前未进行营养支持者;术后出现严重并发症者,临床上普遍存在营养不良营养不良影响患者预后,结 论,临床上许多疾病治疗过程中需要进行营养支持,通过合理营养支持改善患者预后,问题三:如何选择营养支持途径?,Parenteral nutrition,One of the most significant therapeutical advances of the past 50 years Indications:the ability to i
14、ngest necessary nutrients for a time during increased metabolic demands in clinical situations in which enteral(oral)nutrition is not or only partially feasible,Who Needs Parenteral Nutrition?,Any patient requiring nutrition support who has a non-functioning or possible inadequately functioning gast
15、rointestinal tractStart as soon as possible if there is pre-existing malnutrition or metabolic stress and oral/enteral feeding is unlikely to be achieved within 7 days,改善肠道功能,完整性防止饥饿或创伤所致的肠道结构异常增加内脏血流刺激肠道免疫功能,维护机体防御水平,Enteral or Parenteral?,过去1015的年研究发现EN的作用要优于PN,危重病人胃肠功能的损害,肠黏膜萎缩细胞受损,坏死,EN作用:肠通透性、肠
16、动力、分泌功能、屏障功能、免疫功能,Levy B et al.CCM 1998;26:199194Kentigern Thorburn et al.CM;2004,32:24649,EN vs PN in critically ill patients meta-analysis(13RCT Infectious complications),Gramlich L et al.,Nutrition 2004;20:843-848,EN vs PN in critically ill patients meta-analysis(13RCT Mortality),Gramlich L et al
17、.,Nutrition 2004;20:843-848,第二部分,如何合理提供营养支持,临床上不规范的肠外营养 使用仍十分普遍,肠外营养现状,不合理的肠外营养不仅无法达到 预期效果,相反会增加并发症,影响病人预后,如何利用目前已有的知识和技术，使肠外营养作用最大化,方法一:提供合适的营养物质,提供合适的能量 计算各营养底物的需要量选择理想的营养物质,能量代谢,生物体内碳水化合物、蛋白质和脂肪在代谢过程中所伴随的能量释放、转移和利用称为能量代谢,能量代谢与能量需求,能量是维持人体生命活动及内环境稳定最根本需要，也是营养学最基本问题准确了解和测定不同状态下病人的能量消耗是提供合理有效的营养支持及决
18、定营养物质需要量与比例的前提和保证能量在临床营养支持的作用体现在决定营养物质的用量与内容,即确定到底摄入多少热卡,给什么维持机体能量平衡，避免过度喂养或营养不足，这在危重病人尤其重要,能量代谢与能量需求,Energy Balance,Energy In=Energy OutWeight MaintenanceEnergy In Energy OutWeight GainEnergy In Energy OutWeight Loss,机体能量代谢组成,创伤时代谢改变,Stress on energy expenditure and protein losses,180,160,140,120,1
19、00,80,60,(%),REE,40,30,20,10,0,(g),Nitrogen losses,Major burn,Peritonitis,Fracture,Starvation,days,days,Long(1977)Am.J.Clin.Nutr.30,1301-1310,能量消耗及需求,能 量 需 求,病人能量消耗和代谢能力决定能量需求过量营养(Overfeeding)导致并发症和副作用危重病人能量供给目标：保存功能、减少消耗 早期营养支持、控制入量；高代谢期应接受低量营养；恢复期或合成期增加营养摄入量过高的能量供给将导致危重病人感染性并发症以及死亡率的增加，强调限制热量的供给量目
20、前尚无可普遍用于危重病人的EE预测公式,L John Hoffer Am J Clin Nutr.2003 Nov;78(5):906-11,能量供给,合并呼吸衰竭病人，过量葡萄糖与能量供给将使RQ增加，增加脱机难度研究显示：接受呼吸支持的重症病人，提供 10%TEE与低喂养（70%of TEE）或过度喂养（135%of TEE）组相比，可获得最佳的氮平衡效果,Critical care Med 2003;7R:10815,能量消耗的估算方法,Harris-Benedict公式是估算正常情况下机体基础能量消耗的经典公式REE(kcal/d)=66.5+13.8W+5H-6.8A.男REE(kc
21、al/d)=665+9.6W+1.8H-4.7A.女W-体重(kg)H-身高(cm)A-年龄(year),Energy guidelines for nutrition support,Requirements are based on the following guidelines:postoperative 25-30 kcal/kg/daypolytrauma 30-35 kcal/kg/daysepsis 25-40 kcal/kg/dayburns 30-45 kcal/kg/day,“25-30 kcal/kg/day is suitable for most criticall
22、y-ill patients”-ASPEN Guidelines,1993,肠外营养液的基本成分,Role of carbohydrates,glucose requirement,Glucose metabolism during starvation and critical illness,Resting energy expenditure(REE)at different glucose intakes in infants,8,10,12,14,16,18,20,22,24,26,28,35,40,45,50,55,60,65,(kcal/kg bw/d),(g/kg bw.d),
23、Glucose intake,REE,Jones et al.(1993),J.Ped.Surg 28,1121-1125,Disadvantages of sole glucose system,Influence of infusion rate on incidence of hyperglycaemia,Retrospective study in patients not normally predisposed to hyperglycaemia,Rosmarin et al.(1996)Nutr Clin Prac 11,151-156,应激性高血糖与营养支持中的血糖控制,严重创
24、伤感染,儿茶酚胺、皮质醇、胰高糖素释放增加,胰岛素分泌量相对或绝对减少,细胞因子作用（中枢、外周作用）,胰岛素清除增加,应激性高血糖,应激性高血糖,细胞内氧化作用,自由基与过氧化物产生,诱导单核细胞炎症因子表达,细胞因子释放,损伤中性粒细胞与巨噬细胞的杀伤能力及补体功能,应激性高血糖与营养支持中的血糖控制,Intensive insulin therapy in the critically ill patients,Van Den BG.N J Med,2001,应激性高血糖与营养支持中的血糖控制,Van den Berghe G et all.N Engl J Med 2001;345:1
25、359-1367,应激性高血糖与营养支持中的血糖控制,Van den Berghe G et all.N Engl J Med 2001;345:1359-1367,标准：80110mg/dL（Van den berghe）140mg/dL措施：补充外源性胰岛素，减少葡萄糖及非蛋白质热卡的补充量，避免过度喂养（+30%）,应激性高血糖与营养支持中的血糖控制,Van den Berghe G et all.N Engl J Med 2001;345:1359-1367,Van den Berghe G,et all.N Engl J Med 2002;346:1586-8.,Strategy f
26、or using glucose in PN,Optimize delivery but do not exceed oxidative rate-infuse glucose slowly,at 2-4 mg/kg/min 5-(6)g/kg/day)maximum in critically ill patients:3-4 g/kg/dayEnsure normoglycaemia-control serum glucose more aggressively recommended level 120 mg/dLMinimize liponeogenesis-use mixed fue
27、l system of glucose+fat,PN regimen without lipid,A 50 kg patient requires 30 kcal/kg/d total energyTotal energy required=5030=1500 kcal/dayIf only amino acids and glucose are given,and amino acids is given at 1 g/kg/dayProtein calories=504 kcal/g=200 kcalNon-protein calories=1500200=1300 kcalAmount
28、of glucose=1300/4=325 g,Glucose solutions&their osmolarity,双能源系统与单用葡萄糖比较,应激状况下双能源系统优于单用葡萄糖提供必需脂肪酸更好的氮积累，更低的CO2产生危重病人脂肪氧化增加，葡萄糖氧化降低更容易控制血糖,Stoner et al(1983)Br J Surg 70,32-53,Relationship between glucose oxidation and sepsis scores in patients on PN,Relationship between fat oxidation and sepsis scor
29、es in patients on PN,Stoner et al(1983)Br J Surg 70,32-53,Effect of glucose system and mixed fuel system on ventilation,Askanazi et al.(1979)Anesthesiology 51,192,.,Serum glucose profile during PN,Carbohydrate only,Carbohydrate+fat,Hempel et al(1981)Infusionstherapie 3,124-132,Increased lipid fuel d
30、ependence in the critically ill septic patient.Nanni G et al.J Trauma 1984 Jan;24(1):14-30,Patient groups:-Septics:n=246-Non-septic:n=128 Nutrition Regime1)Glucose-TPN 2)Occasional supply of lipids,“()Glucose-only TPN results in excessive CO2 production which may overload CO2 elimination mechanisms
31、of critically ill patients with ventilatory exchange limitations()”,Design:Prospective,controlled trial Patients:Critically ill Nutrition:TPN for 5 days,AA 15%-Group 1(n=8):TPN-G Glucose 75%+Lipid 10%-Group 2(n=8):TPN-LGlucose 15%+Lipid 70%,Glucose-based TPN increases CO2 production.,Effects of isoe
32、nergetic glucose-based or lipid-based PN on glucose metabolism,de novo lipogenesis,and respiratory gas exchanges in critically ill patients.Tappy L,et al.Crit Care Med 1998;26:860-867,TPN-G:TPN-glucose based,TPN-L:TPN-lipid based,=Gastroenterological patients(n=16)=TPN for 2 weeks:Group I:Glucose al
33、one(49 kcal/kg d)Group II:Fat emulsion(60%of the NP-energy,total 51 kcal/kg/d),“Fat in conjunction with glucose may be more effective as an energy source than equicaloric amounts of glucose alone.”,Glucose or fat as a non-protein energy source:a controlled clinical trial in gastroenterological patie
34、nts requiring intravenous nutrition.MacFie J,Gastroenterology 1981;80:103-107,kg,Dual-Energy System:KEY MESSAGES,Avoids hyperglycemia Reduces respiratory and metabolic stress Supports the best possible nitrogen retention Guarantees the delivery of essential fatty acids Facilitates peripheral infusio
35、n due to low osmolarity,Fat requirements,Lipid emulsions,Intralipid,Fatty acid pattern of a soybean oil emulsion,Possible consequences of an excessive intake of omega-6 fatty(linoleic)acids,unbalanced fatty acid pattern in cell membranes modification of the production of lipid mediators(prostaglandi
36、ns,leukotrienes)promotion of immunosuppression and systemic inflammatory reactions(trauma,operation,sepsis),Carpentier et al.,1997,Are soybean oil based emulsions immunosuppressive?,Battistella et al.(1997)J.Trauma 43,52-60Polytrauma patients(APACHE II av.22)Standard glucose containg TPN with no lip
37、id vs.Intralipid(10 days)No difference in CD4/CD8,No lipidIntralipidLength of stay(d)27 39*ICU stay(d)18 29*Days on ventilator15 27*Pneumonia(#)13 22*Total infectious complications 39 72,%of baseline,P=0.02,NK cell activity,Characteristics of MCT vs LCT,Types of lipid emulsions,中/长链脂肪乳剂的优点,大量临床与实验结果
38、证实 中/长链脂肪乳剂在临床各 个领域均有其代谢优势！,JPEN,25(2)Suppl.,2002,Benefits of Structolipid(1),Controlled plasma TG and MCFA levels(Nordenstrm 1995,Flaatten 1995,Kruimel 1997)Reliable source of essential fatty acids As well tolerated as Intralipid(Nordenstrm 1995,Sandstrm 1995,Bellantone 1999)Suitable for long-term
39、PN(Rubin et al 2000),Benefits of Structolipid(2),Rapidly available energy(Sandstrm et al 1995)Improved protein economy compared to LCT and LCT/MCT emulsions(Kruimel et al 1997,Lindgren et al 2001)Excellent mixing properties A handy non-breakable plastic packaging,结构脂肪临床对照研究资料有限结构脂肪具有物理混合中/长链脂肪乳剂结构和生
40、化特征并优于后者从药理角度讲,应用酶学技术,开创了脂肪乳剂新领域,可根据各特殊代谢过程需要设计新型制剂,结构脂肪乳剂临床应用评价,含橄榄油脂肪乳剂具有良好的安全性和有效性,含橄榄油脂肪乳剂应用评价,含橄榄油脂肪乳剂在防止脂质过氧化优于其他长链脂肪乳剂,含橄榄油脂肪乳剂对机体免疫系统影响少,适合于小儿和需长期肠外营养病人,Omegaven as a supplement,Formulation:Lipid emulsionLipid source:Fish oilConcentration:10%Special feature:High content of-3 fatty acidsPurpo
41、se:Supplementation of parenteral nutrition with long-chain-3 fatty acidsPackaging:50&100 ml,glass bottleStorage:0-25CShelf life:18 months,含鱼油的脂肪乳剂在肠外营养时具有良好的安全性;通过调节炎性介质的产生,下调炎性反应,增强机体免疫功能,可改善外科危重病人愈后,总 结,Optimal proportion of lipids in PN,Recommended daily lipid intake:-adult:1.0-2.0 g/kg；-infant:1
42、.0-3.0 g/kg-unstressed patients:30-40%of total calories-stressed patients:40-55%of total caloriesFactors to consider:glucose resistance，impaired respiratory capacityMonitoring:Serum triglycerides Ensure patient is not intolerant to any component of the lipid emulsion,Proteins/Amino acids,The only ma
43、cronutrients containing nitrogen A variety of different functions:Cell and tissue structure:structural proteins Functional roles:transport proteins blood clotting factors receptors enzymes hormones immune globulines muscle contractility.,Proteins/Amino acids,Free AA pool(70 g),Cells,plasma,Proteinsy
44、nthesis(300g/d),Proteolysis(300g/d),Oral intake of proteinsEnteral nutritionParenteral nutrition,Metabolic processes:-neoglucogenesis-neuromediators-cell energyWaste(CO2,urea),Protein/Amino acids,20 different amino acidsNitrogen content(g/L)x 6.25=AA(g/L)Amino acids are linked via peptide bonds,Amin
45、o acid,提供机体合成蛋白质所需的底物 氨基酸利用率和蛋白质合成受其组成影响 目前AA的配比有人乳,全蛋,Rose,FAO,及 血浆游离氨基酸等模式,各种模式优劣难定 临床上常用的氨基酸制剂是平衡型氨基酸 溶液,近年各种治疗型氨基酸输液问世 复方氨基酸液的研制还在不断发展,最佳组 成尚未确定,现有的配方还不是最完善的,Nitrogen requirements,Amino acid/nitrogen dosage?,0.5 1.5 g(max.2 g)/kg/day nitrogen 0.15 0.2 g/kg/dayca.40%essential amino acids high qua
46、lityMax.infusion rate:0.1 g/kg and hour,Role of electrolytes,Electrolyte requirements in PN,Role of trace elements,Daily trace element requirements,Vitamins,Daily vitamin requirements in PN,规范肠外营养输注用全合一形式,全合一的定义,全合一的优点,全部营养物质经混合后同时均匀地输入体内，有利于更好地代谢和利用避免了传统多瓶输注时出现在某段时间中，某种营养剂输入较多，而另一些营养剂输入较少或甚至未输入的不均匀
47、输入现象，减少甚至避免它们单独输注时可能发生副反应和并发症的机会,全合一的优点,3升塑料输液袋壁薄质软，在大气挤压下随着液体的排空逐渐闭合，不需要用进气针，成为一个全封闭的输液系统，使用方便，减轻了护士的监护工作量，也减少被污染或发生气栓的机会各种营养剂在TNA液中互相稀释，渗透压降低，一般可经外周静脉输注，增加了经外周静脉行肠外营养支持的机会,全合一配制的环境和设备要求,建立肠外营养液配制室-肠外营养液配制室的构成-肠外营养液配制室的规章制度层流空气洁净台(超净工作台)肠外营养支持小组组成,RTU Multi-Chamber Bags(MCB),All-in-One,Individual v
48、s standardisedUK-almost 100%AIO by 1995Estimated(1996)80%adults on PN could use standardised regimens Current Perspectives on PN in Adults.BAPEN Working Party 1996,Standardised Regimens,Individualised prescriptions rarely needed(cost&outcome)80%neonatal/paediatric feeds could be standardisedBeecroft
49、 C et al.Clin Nutr 1999 18 83-85,Standardised Regimens,在发达国家，工业化多腔袋逐渐取代医院自配的PN营养液 在瑞士，83%的成人PN采用工业化二腔袋或三腔袋,Pichard C.,et al.Clin Nutr,20(4):345-50,2001,2004年标准全合一PN在瑞士法国和比利时占全部成人PN患者的比例分别为：86,79%,86%.Parenteral Nutrition practices in hospital pharmacies in Switzerland,France,and Belgium.Nutrition 20
50、04;20:528 535.,Single-bottle systems required more items and manipulations.3 CBs satisfied the needs of over 80%of the adult long-term TPN patients for the last 5 years.,Three-chamber bags:Practical Aspects,Clinical Nutrition 2000,19:245-251,Kabiven Central and Peripheral 3CB,Central high(2566 ml),P
