重癥患者血糖如何管理

1、內(nèi)容（outline）,重癥患者應(yīng)激性高血糖重癥患者的血糖管理腸內(nèi)營(yíng)養(yǎng)與血糖管理,重癥患者應(yīng)激性高血糖,1877年Claude Bernard 首次提出“stress hyperglycemia” 是ICU病人很常見(jiàn)的代謝改變，不論既往是否有糖尿病血糖升高與應(yīng)激的嚴(yán)重程度相關(guān),應(yīng)急時(shí)三類(lèi)物質(zhì)代謝特點(diǎn),1, 糖代謝2,脂肪動(dòng)員3,蛋白質(zhì)分解 合成,Crit care clin .2001 jan;17(1);1

2、07-24 Stress-induced hyperglycemia .,ICU內(nèi)應(yīng)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(yīng)激,代謝亢進(jìn),,胰島素受體減少導(dǎo)致胰島素不敏感而非胰島素絕對(duì)量或相對(duì)量減少,SHG的發(fā)生機(jī)理,Crit care clin .2001 jan;17(1);107-24 Stress-induced hyperglycemia .,糖生成? 速度: 5mg/kg/min (正常時(shí)2mg/kg/min)

5、 糖利用? 速度受限，2-3mg/kg/min (即10%GS 150ml/h) 無(wú)效循環(huán): 2-3倍于正常 血糖濃度增加，即應(yīng)激性高血糖（SHG）,SHG的特點(diǎn),,應(yīng)激性高血糖,細(xì)胞內(nèi)氧化作用↑,自由基與過(guò)氧化物產(chǎn)生↑,誘導(dǎo)單核細(xì)胞炎癥因子表達(dá),細(xì)胞因子釋放↑,損傷中性粒細(xì)胞與巨噬細(xì)胞的殺傷能力及補(bǔ)體功能,應(yīng)激性高血糖對(duì)機(jī)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(qiáng)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(qiáng)化治療: 降低MOF-相關(guān)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(jīng)過(guò)驗(yàn)證的方案調(diào)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(yīng)接受葡萄糖作能源,1-2小時(shí)測(cè)量1次血糖,直到穩(wěn)定后改為4小時(shí)1次（1C，

13、修訂） 原推薦: 每30-60mins測(cè)量1次血糖(D)對(duì)從毛細(xì)血管取樣獲得的低血糖的解釋要謹(jǐn)慎,這些測(cè)量可以過(guò)高評(píng)價(jià)動(dòng)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(jié)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(nèi)營(yíng)養(yǎng)與血糖管理,,,控制高血糖,避免低血糖,縮小血糖波動(dòng),,,,預(yù)防高血糖,,減少碳水化合物增加胰島素敏感性,預(yù)防應(yīng)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(yù)防應(yīng)激性高血糖的處理,控制碳水化合物的總量比種類(lèi)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(yù)防應(yīng)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(yīng)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(qiáng) MUFA和SFA毒性很小,對(duì)單核細(xì)胞、內(nèi)皮細(xì)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(yīng)激指標(biāo)的水平,單不飽和脂肪酸膳食通過(guò)緩解氧化應(yīng)激改善糖耐

22、量正常人群的胰島素敏感性。李萍等，中華內(nèi)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(guò)緩解氧化應(yīng)激改善糖耐量正常人群的胰島素敏感性。李萍等，中華內(nèi)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(guò)緩解氧化應(yīng)激改善糖耐量正常人群的胰島素敏感性。李萍等，中華內(nèi)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(duì)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(xiàn)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(yíng)養(yǎng)指南對(duì)腸內(nèi)營(yíng)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(nèi)營(yíng)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(fēng)險(xiǎn)；…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