1、內容（outline）,重癥患者應激性高血糖重癥患者的血糖管理腸內營養(yǎng)與血糖管理,重癥患者應激性高血糖,1877年Claude Bernard 首次提出“stress hyperglycemia” 是ICU病人很常見的代謝改變，不論既往是否有糖尿病血糖升高與應激的嚴重程度相關,應急時三類物質代謝特點,1, 糖代謝2,脂肪動員3,蛋白質分解 合成,Crit care clin .2001 jan;17(1);1

2、07-24 Stress-induced hyperglycemia .,ICU內應激性高血糖（SHG）發(fā)生率高于普通病房,Non-critically ill medical/surgical: 33-38%1,2Intensive care units (ICU): 29% - 100%3Episodes of glucose >110 mg/dL: 100%Episodes of glucose >200 m

3、g/dL: 31%Mean glucose >145 mg/dL: 39%,Umpierrez G et al. J Clin Endocrinol Metabol 2002,87:978-982Levetan CS et al. Diabetes Care 1998;21:246-249.Krinsley JS. Mayo Clin Proc 2003;78:1471-1478.Falciglia M et al. Cr

4、it Care Med 2009; 37:3001-3009.,甲狀腺素?兒茶酚胺?胰島素?胰高血糖素?,應激,代謝亢進,,胰島素受體減少導致胰島素不敏感而非胰島素絕對量或相對量減少,SHG的發(fā)生機理,Crit care clin .2001 jan;17(1);107-24 Stress-induced hyperglycemia .,糖生成? 速度: 5mg/kg/min (正常時2mg/kg/min)

5、 糖利用? 速度受限，2-3mg/kg/min (即10%GS 150ml/h) 無效循環(huán): 2-3倍于正常 血糖濃度增加，即應激性高血糖（SHG）,SHG的特點,,應激性高血糖,細胞內氧化作用↑,自由基與過氧化物產生↑,誘導單核細胞炎癥因子表達,細胞因子釋放↑,損傷中性粒細胞與巨噬細胞的殺傷能力及補體功能,應激性高血糖對機體的影響,,,,,,,,Normo

6、glycemia Known diabetes New Hyperglycemia,1.7%,3.0%,16.0%*,Mortality (%),P < 0.01,Umpierrez GE et al. J Clin Endocrinol Metabol 2002;87:978-982.,Hyperglycemia: an independent marker of in-hospital mort

7、ality in patients with undiagnosed diabetes,Total Inpatient Mortality,,Krinsley JS. Mayo Clin Proc 2003;78:1471-1478.,,Hyperglycemia and mortality in the ICU,Mix- ICU (Stamford)回顧分析: Oct.1, 1999~Apr.4, 2002，n=1826,1 Fur

8、nary AP, et al. Ann Thorac Surg 1999;67:352–362. 2 Van den Berghe et al. N Engl J Med 2001;345:1359-1367.3 Krinsley JS et al. Chest. 2006;129:644-650.4 Newton CA et al. Endocr Prac 2006:12(suppl 3):43-48.,Cost Savings As

9、sociated with Managing Hospital Hyperglycemia,Furnary1 – $5,580 per CABG patient per stay (length of stay and incidence of wound infection)Van den Berghe2 – € 2,638 per patient per ICU stay (average ICU stay: 8.6 days c

10、onventional treatment vs. 6.6 days intensive treatment)Krinsley3 – $1.3M annual cost savings for a 305-bed community based hospital (14-bed ICU)Newton4 - $1.9 M annual cost saving for a 750 bedtertiary care center in

11、North Carolina (non-ICU).Nurse case manager-based program,重癥患者的血糖管理,Intensive insulin therapy in the critically ill patients,1548 ICU 病人 研究期間 12 months 傳統(tǒng)治療: 血糖 180-210 mg/dl 強化治療: 血糖 80-110 mg/dl 胰島素: 0-50 IU/

12、h iv 總死亡率: 10.6% vs. 20.2% (p=0.005),強化治療: 降低MOF-相關的死亡率!,van den Berghe G, et al. N Engl J Med. 2001;345:1359–67,2008年指南－血糖控制,使用經過驗證的方案調整胰島素的劑量,使得血糖<150mg/dl（2C，新增）接受胰島素的患者應接受葡萄糖作能源,1-2小時測量1次血糖,直到穩(wěn)定后改為4小時1次（1C，

13、修訂） 原推薦: 每30-60mins測量1次血糖(D)對從毛細血管取樣獲得的低血糖的解釋要謹慎,這些測量可以過高評價動脈或血漿的血糖水平（1B，新增）,Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation (NICE-SUGAR) －－－a collaboration of the Australi

14、an and New Zealand Intensive Care Society Clinical Trials Group,,背景,方法,,,,兩組患者血糖水平,Outcome,,,,亞組分析,結論（Conclusions）,In this large, international, randomized trial, we found that intensive glucose control increased mortali

15、ty among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.),ESPEN PN Guideline

16、s 2009,Indication of PN:Patients should be fed as starvation or underfeeding in ICU patients = associated with increased morbidity and mortality (C)All patients not expected to be on normal nutrition within 3d should r

17、eceive PN within 24-48h if EN = contraindicated or not tolerated (C)Indication for PN supplementary to ENAll patients receiving less than their targeted EN after 2days should be considered for supplementary PN (C)Veno

18、us access:Central venous access = often required (full coverage of nutritional needs ? high osmolarity PN) (C)Peripheral access: for low osmolarity (<850mOsm/L) (C)PN admixtures should be administered as a complet

19、e all-in-one bag (B),Singer et al.ESPEN guidelines on PN: Intensive Care, Clinical Nutrition 2009; in press,,,2012 sepsis guideline,血糖與重癥患者的死亡率,,,,,,↑死亡,,腸內營養(yǎng)與血糖管理,,,控制高血糖,避免低血糖,縮小血糖波動,,,,預防高血糖,,減少碳水化合物增加胰島素敏感性,預防應激

20、性高血糖的處理,碳水化合物減少外源性葡萄糖輸入總量 < 200g/day2. 減慢外源性葡萄糖輸入速度<3mg/kg/min3.減少葡萄糖供能比例（7：3?6：4）,預防應激性高血糖的處理,控制碳水化合物的總量比種類更為重要,ADA和DNSG/EASD指南推薦,,減少碳水化合物增加胰島素敏感性,預防應激性高血糖的發(fā)生,改變脂肪組分,,增加胰島素敏感性,改變脂肪組分,,改變血脂組分,降低氧應激,,,C,C,C,C,C,

21、C,C,C,C,C,C,C,C,C,C,C,C,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,H,O,C,O,-,PUFA雙鍵多，易受攻擊,,,,,,,,,? - 6,PUFA的毒性最強 MUFA和SFA毒性很小,對單核細胞、內皮細胞的毒性,MUFA減輕氧自由基損傷,MUFA降低8-異前列腺素F2α等氧化應激指標的水平,單不飽和脂肪酸膳食通過緩解氧化應激改善糖耐

22、量正常人群的胰島素敏感性。李萍等，中華內分泌代謝雜志，2010，Vol26，No.10,MUFA增加胰島素敏感性,單不飽和脂肪酸膳食通過緩解氧化應激改善糖耐量正常人群的胰島素敏感性。李萍等，中華內分泌代謝雜志，2010，Vol26，No.10,*P<0.01,MUFA影響血脂,*,*,* P<0.05,高單不飽和脂肪酸(MUFA)飲食降低總膽固醇(TC)水平 和低密度脂蛋白-膽固醇

23、(LDL-C)水平。,單不飽和脂肪酸膳食通過緩解氧化應激改善糖耐量正常人群的胰島素敏感性。李萍等，中華內分泌代謝雜志，2010，Vol26，No.10,Paniagua JA, et al. A MUFA-rich diet improves posprandial glucose, lipid and GLP-1 responses in insulin-resistant subjects. J Am Coll Nutr,2007；

24、26（5）：434-44.,MUFA對糖尿病患者血糖與血脂的影響,,,,含MUFA的膳食降低HBA1c、空腹血糖、血糖和胰島素曲線下面積含MUFA的膳食改善胰島素抵抗、減少GLP-1、降低空腹胰島素原水平、提高HDL-c水平、提高Apo A-1和Apo B100,營養(yǎng)指南對腸內營養(yǎng)配方的建議,ESPEN Guidelines，2006 低碳水化合物、高單不飽和脂肪酸配方的腸內營養(yǎng)能更有助于血糖控制；…有助于減少糖尿病病人心

25、血管風險；…有助于降低血甘油三酯和總膽固醇水平,糖尿病配方與普通配方,StandardHigh in rapidly-digested carbohydratesLow in fatLow in fiberMay compromise glycemic control in patients with diabetesMay require more time and medications to maintain blood

26、 glucose levels in good control,Diabetes SpecificModified carbohydratesModified fat: favor inclusion of monounsaturated (MUFA) fatsHigh in fiberEnable better glycemic control due to special formulationMay reduce n