重症患者血糖如何管理

内容（outline）重症患者应激性高血糖重症患者的血糖管理肠内营养与血糖管理重症患者应激性高血糖1877年ClaudeBernard首次提出“stresshyperglycemia”是ICU病人很常见的代谢改变，不论既往是否有糖尿病血糖升高与应激的严重程度相关应急时三类物质代谢特点1,糖代谢2,脂肪动员3,蛋白质分解合成Critcareclin.2001jan;17(1);107-24Stress-inducedhyperglycemia.ICU内应激性高血糖（SHG）发生率高于普通病房Non-criticallyillmedical/surgical:33-38%1,2Intensivecareunits(ICU):29%-100%3‐Episodesofglucose110mg/dL:100%‐Episodesofglucose200mg/dL:31%‐Meanglucose145mg/dL:39%1.UmpierrezGetal.JClinEndocrinolMetabol2002,87:978-9822.LevetanCSetal.DiabetesCare1998;21:246-249.3.KrinsleyJS.MayoClinProc2003;78:1471-1478.4.FalcigliaMetal.CritCareMed2009;37:3001-3009.代谢亢进胰岛素受体减少导致胰岛素不敏感而非胰岛素绝对量或相对量减少SHG的发生机理Critcareclin.2001jan;17(1);107-24Stress-inducedhyperglycemia.糖生成速度:5mg/kg/min(正常时2mg/kg/min)糖利用速度受限，2-3mg/kg/min(即10%GS150ml/h)无效循环:2-3倍于正常血糖浓度增加，即应激性高血糖（SHG）SHG的特点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对机体的影响0102030NormoglycemiaKnowndiabetesNewHyperglycemia1.7%3.0%16.0%*Mortality(%)P0.01UmpierrezGEetal.JClinEndocrinolMetabol2002;87:978-982.Hyperglycemia:anindependentmarkerofin-hospitalmortalityinpatientswithundiagnoseddiabetes•TotalInpatientMortalityKrinsleyJS.MayoClinProc2003;78:1471-1478.~2xMortalityRate(%)MeanGlucose(mg/dL)80-99100-119120-139140-159160-179180-199200-249250-29930051015202530354045~4x~3xHyperglycemiaandmortalityintheICUMix-ICU(Stamford)回顾分析:Oct.1,1999~Apr.4,2002，n=18261FurnaryAP,etal.AnnThoracSurg1999;67:352–362.2VandenBergheetal.NEnglJMed2001;345:1359-1367.3KrinsleyJSetal.Chest.2006;129:644-650.4NewtonCAetal.EndocrPrac2006:12(suppl3):43-48.CostSavingsAssociatedwithManagingHospitalHyperglycemiaFurnary1–$5,580perCABGpatientperstay(lengthofstayandincidenceofwoundinfection)VandenBerghe2–€2,638perpatientperICUstay(averageICUstay:8.6daysconventionaltreatmentvs.6.6daysintensivetreatment)Krinsley3–$1.3Mannualcostsavingsfora305-bedcommunitybasedhospital(14-bedICU)Newton4-$1.9Mannualcostsavingfora750bedtertiarycarecenterinNorthCarolina(non-ICU).Nursecasemanager-basedprogram11重症患者的血糖管理Intensiveinsulintherapyinthecriticallyillpatients•1548ICU病人•研究期间12months•传统治疗:血糖180-210mg/dl•强化治疗:血糖80-110mg/dl•胰岛素:0-50IU/hiv•总死亡率:10.6%vs.20.2%(p=0.005)强化治疗:降低MOF-相关的死亡率!vandenBergheG,etal.NEnglJMed.2001;345:1359–672008年指南－血糖控制使用经过验证的方案调整胰岛素的剂量,使得血糖150mg/dl（2C，新增）接受胰岛素的患者应接受葡萄糖作能源,1-2小时测量1次血糖,直到稳定后改为4小时1次（1C，修订）原推荐:每30-60mins测量1次血糖(D)对从毛细血管取样获得的低血糖的解释要谨慎,这些测量可以过高评价动脉或血浆的血糖水平（1B，新增）NormoglycemiainIntensiveCareEvaluation–SurvivalUsingGlucoseAlgorithmRegulation(NICE-SUGAR)－－－acollaborationoftheAustralianandNewZealandIntensiveCareSocietyClinicalTrialsGroup背景方法两组患者血糖水平Outcome亚组分析结论（Conclusions）Inthislarge,international,randomizedtrial,wefoundthatintensiveglucosecontrolincreasedmortalityamongadultsintheICU:abloodglucosetargetof180mgorlessperdeciliterresultedinlowermortalitythandidatargetof81to108mgperdeciliter.(ClinicalTrials.govnumber,NCT00220987.)ESPENPNGuidelines2009IndicationofPN:PatientsshouldbefedasstarvationorunderfeedinginICUpatients=associatedwithincreasedmorbidityandmortality(C)Allpatientsnotexpectedtobeonnormalnutritionwithin3dshouldreceivePNwithin24-48hifEN=contraindicatedornottolerated(C)IndicationforPNsupplementarytoENAllpatientsreceivinglessthantheirtargetedENafter2daysshouldbeconsideredforsupplementaryPN(C)Venousaccess:Centralvenousaccess=oftenrequired(fullcoverageofnutritionalneedshighosmolarityPN)(C)Peripheralaccess:forlowosmolarity(850mOsm/L)(C)PNadmixturesshouldbeadministeredasacompleteall-in-onebag(B)EnergyDuringacuteillness:provideenergyascloseaspossibletomeasuredenergyexpenditure(B)Inabsenceofindirectcalorimetry:25kcal/kgBW/dincreasingtotargetoverthenext2-3days(C)AminoacidsBalancedaminoacidmixtureat~1.3-1.5g/kgIBW/dinconjunctionwithadequateenergysupply(B)GlutaminAAsolutionshouldcontain0.2-0.4g/kg/dofL-gln(e.g.0.3-0.6g/kg/dalanyl-glutaminedipeptide)(A)CarbohydratesMinimalamount:~2g/kg/d(B)Hyperglycemia(glc10mmol/L)shouldbeavoidedThereisahigherincidenceofseverehypoglycemiainpatientstreatedtothetighterlimits(A)LipidsShouldbeanintegralpartofPN(B)(fordetailsseenextpage)MicronutrientsAllPNprescriptionsshouldincludeadailydoseofmultivitaminsandoftraceelements(C)ElectrolytesHighlyvariablerequirementsshouldbedeterminedbyplasmaelectrolytemonitoringSingeretal.ESPENguidelinesonPN:IntensiveCare,ClinicalNutrition2009;inpress2012sepsisguideline血糖与重症患者的死亡率低血糖高血糖血糖波动↑死亡肠内营养与血糖管理控制高血糖避免低血糖缩小血糖波动预防高血糖•减少碳水化合物•增加胰岛素敏感性预防应激性高血糖的处理碳水化合物1.减少外源性葡萄糖输入总量200g/day2.减慢外源性葡萄糖输入速度3mg/kg/min3.减少葡萄糖供能比例（7：36：4）预防应激性高血糖的处理控制碳水化合物的总量比种类更为重要ADA和DNSG/EASD指南推荐•减少碳水化合物•增加胰岛素敏感性预防应激性高血糖的发生改变脂肪组分增加胰岛素敏感性改变脂肪组分改变血脂组分降低氧应激CCCCCCCCCCCCCCCCCHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHOCO-PUFA双键多，易受攻击-6OeOeOe•PUFA的毒性最强•MUFA和SFA毒性很小对单核细胞、内皮细胞的毒性MUFA减轻氧自由基损伤MUFA降低8-异前列腺素F2α等氧化应激指标的水平单不饱和脂肪酸膳食通过缓解氧化应激改善糖耐量正常人群的胰岛素敏感性。李萍等，中华内分泌代谢杂志，2010，Vol26，No.10MUFA增加胰岛素敏感性单不饱和脂肪酸膳食通过缓解氧化应激改善糖耐量正常人群的胰岛素敏感性。李萍等，中华内分泌代谢杂志，2010，Vol26，No.10*P0.01MUFA影响血脂***P0.05高单不饱和脂肪酸(MUFA)饮食降低总胆固醇(TC)水平和低密度脂蛋白-胆固醇(LDL-C)水平。单不饱和脂肪酸膳食通过缓解氧化应激改善糖耐量正常人群的胰岛素敏感性。李萍等，中华内分泌代谢杂志，2010，Vol26，No.10Paniagu