ICU患者血糖的控制

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/3,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/3,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/3,*,ICU患者血糖的控制,ICU患者血糖的控制ICU患者血糖的控制,血糖的来源和去路,血糖,3.89 6.11,CO,2,+H,2,O,其他糖,肝，肌糖原,脂肪，氨基酸等,肝糖原,非糖物质,食物糖,消化吸收,分解,糖异生,氧化分解,糖原合成,磷酸戊糖途径等,脂类，氨基酸代谢,2020/11/3,2,血糖水平的调节,升糖激素：,胰高血糖素，肾上腺皮质激素，肾上腺髓质激素，生长激素，甲状腺素，性激素，,降糖激素：,胰岛素(体内唯一降低血糖的激素),2020/11/3,3,胰岛素与血糖,胰腺胰岛细胞分泌,对糖代谢的调节：促进组织细胞对葡萄糖的摄取和利用；加速葡萄糖合成为糖原，储存于肝和肌肉；抑制糖异生；促进葡萄糖转变为脂肪酸，储存于脂肪组织,2020/11/3,4,血糖水平异常,糖代谢障碍血糖水平紊乱,一高血糖,糖尿病：,type1，type 2，,特异型糖尿病，,妊娠糖尿病,应激状态下的高血糖状态,二低血糖,2020/11/3,5,应激状态下发生高血糖的原因,反向调节激素产生增加,诱发炎症反应的细胞因子产生,增多，诱发胰岛素抵抗,外源性因素的作用进一步促使高血,糖的发生（激素，含糖液体）,高血糖,2020/11/3,6,高血糖的危害,降低免疫功能和增加感染性并发症，成为独立因素影响危重症预后,长期慢性高血糖所致心脑肾血管损害，视网膜病变和神经病变,减慢伤口愈合,高血糖毒性,2020/11/3,7,患者血糖异常,应激状态下的高血糖状态合并胰岛素抵抗,分解代谢加速,糖异生作用加强,激活机体神经内分泌系统,致使代谢激素(儿茶酚胺、皮质醇、胰高血糖素、生长激素) 分泌异常,细胞因子大量释放和胰岛素抵抗,2020/11/3,8,ICU患者高血糖的危害,Hyperglycemia occurs in up to 90 % of critically ill patients and is associated with increased morbidity and mortality in virtually all subgroups of intensive care unit (ICU) patients.,超过90 的危重病人会发生高血糖，并且会增加几乎所有亚组ICU患者的发病率和死亡率,2020/11/3,9,最佳目标血糖水平？,是否血糖水平在正常范围内就能降低死亡率？,什么样的血糖水平可使ICU患者获益最大？,2020/11/3,10,血糖控制史上的“里程碑”,2009年,2008年,2001年,NICE SUGAR研究,Surviving Sepsis,Campaign,强化血糖控制,2020/11/3,11,血糖控制-强化胰岛素治疗,前瞻性随机对照试验,外科ICU机械通气成人患者1548例,随机分为：,强化胰岛素治疗组,传统治疗组,强化胰岛素治疗组,维持血糖80110 mg/dL (4.46.1 mmol/L),传统治疗组,血糖高于215mg/dL(12 mmol/L)输注胰岛素,维持在180200mg/dL(1011mmol/L),.,Intensive insulin therapy in the critically ill patients,(危重患者的强化胰岛素治疗),Van den Berghe G, et al.N Engl J Med 2001; 345: 13591367.,2020/11/3,12,血糖控制-强化胰岛素治疗,平均跟踪,23,天结局,强化胰岛素,传统治疗,ICU死亡,5%,8%,住院死亡,7%,11%,ICU留住5天以上,11%,16%,机械通气14天以上,8%,12%,需血滤/透析肾衰,5%,8%,血行感染,4%,8%,危重病多发性神经病,29%,52%,2020/11/3,13,血糖控制-强化胰岛素治疗,Van den Berghe G, et al: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345: 13591367.,入住后天数 入院后天数,住院生存率,ICU生存率,2020/11/3,14,血糖控制 -强化胰岛素治疗,随后分析表明，尽管将血糖控制在80110 mg/dL (4.46.1 mmol/L)最佳,但是与高血糖比较，目标为血糖,150 mg/dL (8.3 mmol/L)也能改善预后,In conclusion, the use of exogenous insulin to maintain blood glucose at a level no higher than 110 mg per deciliter reduced morbidity and mortality among critically ill patients in the surgical intensive care unit, regardless of whether they had a history of diabetes,无论有无糖尿病病史，应用胰岛素将血糖水平控制在110 mg/dL以下能降低外科ICU患者死亡率,Van den Berghe G, et al: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345: 13591367.,2020/11/3,15,2008-,Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock,1. We recommend that, following initial stabilization, patients with severe sepsis and hyperglycemia who are admitted to the ICU receive IV insulin therapy to reduce blood glucose levels (Grade 1B).,2. We suggest use of a validated protocol for insulin dose adjustments and targeting glucose levels to the,150 mg/dl range (Grade 2C).,3. We recommend that all patients receiving intravenous insulin receive a glucose calorie source and that blood glucose values be monitored every 12 hours until glucose values and insulin infusion rates are stable and then every 4 hours thereafter (Grade 1C).,4. We recommend that low glucose levels obtained with point-of-care testing of capillary blood be interpreted with caution, as such measurements may overestimate arterial blood or plasma glucose values (Grade 1B).,2020/11/3,16,2008-,Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock,1.We recommend that, following initial stabilization, patients with severe sepsis and hyperglycemia who are admitted to the ICU receive IV insulin therapy to reduce blood glucose levels (Grade 1B),我们建议，初步稳定后，发生高血糖的严重脓毒症的,ICU,患者应接受静脉胰岛素治疗来降低血糖水平,(Grade 1B),2020/11/3,17,2.We suggest use of a validated protocol for insulin dose adjustments and targeting glucose levels to the,150 mg/dl range (8.3mmol/L) (Grade 2C),我们建议使用有效的方案来调整胰岛素剂量，目标血糖水平为,150 mg/dl (8.3mmol/L) (Grade 2C),2008-,Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock,2020/11/3,18,3.We recommend that all patients receiving intravenous insulin receive a glucose calorie source and that blood glucose values be monitored every 12 hours until glucose values and insulin infusion rates are stable and then every 4 hours thereafter (Grade 1C),我们建议，所有接受静脉注射胰岛素患者应接受葡萄糖为热量来源，并且每1-2小时监测血糖值，直到血糖水平和胰岛素输注率稳定后每4小时监测血糖值,(Grade 1C),2008-,Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock,2020/11/3,19,4. We recommend that low glucose levels obtained with point-of-care testing of capillary blood be interpreted with caution, as such measurements may overestimate arterial blood or plasma glucose values (Grade 1B),由手指血糖测得的低血糖水平应持谨慎态度，因为这种测量获得的数值可能高于动脉血或血清值,(Grade 1B),2008-,Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock,2020/11/3,20,Can controlling blood sugar levels in the ICU save your life?,Tue Mar 24, 2009Landmark studies published in New England,Journal of Medicine and CMAJ（Canadian Medical Association Journal）,This is the question a team of critical care physician researchers at VGH set out to answer several years ago. Their work is published today in the,New England Journal of Medicine,and,Canadian Medical Association Journal (CMAJ),. The results call for an urgent review of international clinical guidelines.,L to R: Investigator Dr. Vinay Dhingra discusses the SUGAR study with research co-ordinators Susan Logie and Laurie Smith along with Canadian project manager Denise Foster,.,控制血糖水平能拯救ICU患者的生命吗？,发表在新英格兰和HCAMJ杂志上研究的里程碑,2020/11/3,21,NICE SUGAR研究 ：,Background 背景,A parallel-group, randomized, controlled trial involving adult medical and surgical patients admitted to the ICUs of 42 hospitals: 38 academic tertiary care hospitals and 4 community hospitals,Involving 42 hospitals from four countries and two continents,Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control,大样本，随机，对照试验,42家医院的外科和内科成人ICU患者，38学院的三级保健医院，4个社区医院,四个国家和两个大洲,6104例随机分成2组，强化胰岛素治疗组3054例和传统治疗组3050例,2020/11/3,22,NICE SUGAR研究 ：,Two target ranges groups,强化胰岛素治疗组the intensive (i.e., tight) control,目标血糖水平81108 mg/dL (4.56.0 mmol/L),传统治疗组the conventional control,目标血糖水平180mg/dL(10.0mmol/L)及以下,2020/11/3,23,方法,Control of blood glucose was achieved with the use of an intravenous infusion of insulin in saline.,静脉注射胰岛素控制血糖,In the group of patients assigned to undergo conventional glucose control, insulin was administered if the blood glucose level exceeded 180 mg per deciliter (10.0 mmol per liter); insulin administration was reduced and then discontinued if the blood glucose level dropped below 144 mg per deciliter (8.0 mmol per liter).,在传统治疗组如果血糖水平超过10.0mmol/L;应用胰岛素。如果血糖水平低于8.0mmol/L胰岛素用量减少，然后停止,2020/11/3,24,NICE SUGAR研究 ：结论,经过总计6030例患者的校验，强化血糖控制在81-108 mg/dl者的所有主要或次要考察指标都显著差于常规治疗组（血糖述评180 mg/dl）,强化血糖控制组,90天病死率,明显升高 (27.5% vs. 24.9%, p = 0.02， 根据危险因素进行校正后病死率仍有显著差异；强化血糖控制组,存活时间,缩短 (HR 1.11, 95%CI 1.01 1.23, p = 0.04，强化血糖控制组死于心血管病因的比例更高) ；强化血糖控制组发生,严重低血糖,的患者比例明显升高 (6.8% vs. 0.5%, OR 14.7, 95%CI 9.0 25.9, p 30 mmol/L，先皮下注射 5 u，再静脉泵入,2020/11/3,47,应用肠内营养的患者,以营养泵输入肠内营养液，固定输入速度,血糖偏高患者可选用适合糖尿病患者的营养剂（果糖，如：瑞代）,行CRRT的患者,CRRT可影响血糖水平,选用无糖配方的置换液,CRRT时加强血糖检测，CRRT时每2小时测一次血糖,2020/11/3,48,恢复,三餐,饮食的患者,危重期患者不进食血糖控制较容易,血糖波动较小,而患者恢复进食后要加用三餐胰岛素,可以按0. 41. 0 U/ kg 给予胰岛素总量,40 %50 %作为胰岛素基础量;或者按0. 2 U/ kg 胰岛素作为基础量,余下5060 %按早、中、晚各1/ 3 ,于3 餐前以追加剂量的形式输入皮下,2020/11/3,49,Protocol 控制方案,Manual Protocol,Computer-based Insulin Infusion Protocol,efficient,low rate of hypoglycemic episodes,2020/11/3,50,2020/11/3,51,胰岛素输入方案：血糖目标,80150 mg/dL（,4.48.3,mmol/dl,）,起始血糖浓度,100-150,mg/dL（,4.48.3,mmol/dl,）,1U/h,151-200,mg/dL （,8.311,mmol/dl,）,2U/h,201-250,mg/dL （,1113.7,mmol/dl,）,2U iv, 然后2U/h,251-300,mg/dL （,13.716.5,mmol/dl,）,4U iv, 然后2U/h,300,mg/dL （,16.5,mmol/dl,）,4U iv, 然后4U/h,2020/11/3,52,*Footnote,Source:Source,如果葡萄糖，肠内或肠外输入速度下降（或全肠外营养要换成肠内），胰岛素输入速度减半,营养支持的患者,当治疗ARDS等疾病时，可将,氢化可的松每日总量持续静脉泵入,应用,皮质类固醇的患者,继续之前的胰岛素用法和口服降糖药物用法,按调整方案调整胰岛素用量，如果血糖6小时仍未达标或速度超过10U/h，,请通知医生,如果缩血管药物（肾上腺素，去甲肾上腺素，血管加压素，.苯肾上腺素，,多巴胺），皮质类固醇或者连续静脉血液透析停用，将之前泵入速度减半,并1小时内复测血糖,2020/11/3,53,2020/11/3,54,血糖监测,每,12,小时然后每,24,小时检查血钾浓度,如果血糖,5.5,则复查,如果血糖,27.5,mmol/dl,或者与临床情况不符，送实验,室复查,如果临床状况显著改变则恢复为,Q1h,（缩血管药,物，,CRRT,，营养支持，糖皮质激素）,血糖稳定（至少,2,次测得值达标）前每小时测一次，,然后改为,Q2h,，一旦达标达,12h,，减为,Q4h,2020/11/3,55,调整方案,血糖浓度,0.13.9 U/h,46.9 U/h,710 U/h,10 U/h,5.5时，胰岛素减半输入，Q1h复测,2.73.8,停用胰岛素，,20,ml 50%葡萄糖IV，15min复测血糖，必要时重复,至少1h后再用胰岛素，通知医生,如果没有营养，可用5%葡萄糖滴注,当血糖5.5时，胰岛素减半输入，Q1h复测,3.84.4,停用胰岛素， 1h复测血糖，若血糖5.5，减半输入， 1h复测血糖,停用胰岛素， 1h复测血糖，若血糖5.5，减少2U/h输入， 1h复测血糖,停用胰岛素， 1h复测血糖，若血糖5.5，减少3U/h输入， 1h复测血糖,停用胰岛素， 1h复测血糖，若血糖5.5，减少4U/h输入， 1h复测血糖,4.48.3,血糖下降2.7，停用30min，复查，若4.4，减半输入，1h复测血糖,血糖下降2.7，停用30min，复查，若4.4，减少2U/h输入，1h复测血糖,血糖下降2.7，停用30min，复查，若4.4，减少3U/h输入，1h复测血糖,血糖下降2.7，停用30min，复查，若4.4，减少4U/h输入，1h复测血糖,血糖下降1.32.7，减半输入，1h复测血糖,血糖下降1.32.7，减少2U/h输入，1h复测血糖,血糖下降1.32.7，减少3U/h输入，1h复测血糖,血糖下降1.32.7，减少4U/h输入，1h复测血糖,若不是上述2种情况，则输入速度不变，若血糖连续2次在此浓度范围内，则改为Q2h,若不是上述2种情况，则输入速度不变，若血糖连续2次在此浓度范围内，则改为Q2h,若不是上述2种情况，则输入速度不变，若血糖连续2次在此浓度范围内，则改为Q2h,若不是上述2种情况，则输入速度不变，若血糖连续2次在此浓度范围内，则改为Q2h,2020/11/3,56,低血糖,正常空腹血糖3.3mmol/L(60mg/dl),可疑低血糖空腹血糖2.5,3.3mmol/L,低血糖空腹血糖2.5mmol/L(45mg/dl）,低血糖症出现相应症状和体征,2020/11/3,57,神经系统症状,脑细胞所需能量几乎完全来自葡萄糖,肝糖原耗竭，酮体生成需一定时间,脑功能障碍症状：认知障碍，抽搐，昏迷,交感神经兴奋症状：心悸，出汗，焦虑，肌肉颤抖，饥饿感,反复发作，持续时间长：神经元变性坏死，脑水肿，永久性脑功能障碍，死亡,2020/11/3,58,临床表现的严重程度,低血糖的浓度（血糖2.2mmol/L 可以导致神经系统不可逆损害）,低血糖的发生速度和持续时间,机体对低血糖的反应性,年龄,无知觉性低血糖：老年人，慢性低血糖病人,2020/11/3,59,低血糖的治疗,轻者口服糖水或糖果,重者静脉注射50%葡萄糖40100ml，必要时重复或继以5% 10%葡萄糖静脉滴注，必要时加用氢化可的松100mg静脉滴注和（或）胰高血糖素0.5 1mg肌肉或静脉注射,2020/11/3,60,谢谢观赏,