ICU患者血糖的控制精品课件

1、ICU患者血糖的监测与管理,血糖的来源和去路,血糖 3.89 6.11,CO2+H2O,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,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),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,血糖水平异常,糖代谢障碍血糖水平紊乱 一高血糖 糖尿

2、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,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,高血糖的危害,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,ICU患者高血糖的危害,Hyperglycemia occurs in up to 90 % of critically i

3、ll 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,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？,血糖控制史上的“里程碑”,2009年,2008年,2001年,NICE SUGAR研究,Surviving Sepsis Campaign,强

4、化血糖控制,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: 135913

5、67.,血糖控制-强化胰岛素治疗,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,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

6、 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

7、Berghe G, et al: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345: 13591367.,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 an

8、d 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 intrave

9、nous 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 bl

10、ood be interpreted with caution, as such measurements may overestimate arterial blood or plasma glucose values (Grade 1B).,2008-Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock,1.We recommend that, following initial stabilization, patients with sev

11、ere 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),2.We suggest use of a validated protocol for insulin dose adjustments and targeting glucose levels to the 150 mg/dl r

12、ange (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,3.We recommend that all patients receiving intravenous insulin receive a glucose calorie source and that

13、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 manage

14、ment of severe sepsis and septic shock,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

15、 1B),2008-Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock,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）,Th

16、is 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 guideline

17、s.,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,NICE SUGAR研究 ：Background 背景,A parallel-group, randomized, controlled trial involv

18、ing 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

19、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,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(

20、10.0mmol/L)及以下,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 pe

21、r 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,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

22、） 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 0.001)；同时，强化血糖控制组在 90天内ICU住院日及总住院日；新发单一或多器官功能衰竭患者比例；机械通气时间，肾脏替代时间，血培养阳性率和输血比例等诸多方面也没有显示出和常规治

23、疗组之间的差异。,死亡率和生存时间,Ninety days after randomization, 829 of 3010 patients (27.5%) in the intensive-control group had died, as compared with 751 of 3012 patients (24.9%) in the conventional-control group 随机分组后90天， 强化胰岛素治疗组3010例中的829例（ 27.5 ）死亡，而传统治疗组3012例中的751例（ 24.9 ）死亡 The median survival time was lo

24、wer in the intensive-control group than in the conventional-control group 平均生存时间强化胰岛素治疗组低于传统治疗组,90天存活率,The probability of survival, which at 90 days was greater in the conventional-control group than in the intensive-control group (hazard ratio, 1.11; 95% confidence interval, 1.01 to 1.23; P = 0.03)

25、. 90天存活率强化胰岛素组高于传统治疗组,ICU留住时间,During the 90-day study period, there was no significant difference between the two groups in the median length of stay in the ICU 在90天的研究期间，2组ICU平均留住时间没有显著差异,器官功能衰竭，机械通气时间和肾脏替代疗法,The number of patients in whom new single or multiple organ failures developed were simila

26、r with intensive and conventional glucose control (P = 0.11) 新发生的单个或多器官功能衰竭，2组相似 There was no significant difference between the two groups in the numbers of days of mechanical ventilation and renal replacement therapy 机械通气时间和肾脏替代疗法没有显著差异,subgroup analyses,With respect to 90-day mortality, subgroup

27、analyses suggested no significant difference 90天死亡率亚组间没有显著差异,最佳目标血糖水平,In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg(10.0 mmol or less per liter) or less per deciliter resulted in l

28、ower mortality than did a target of 81 to 108 mg per deciliter(4.5 to 6.0 mmol per liter). 这次大样本国际随机实验显示：在ICU患者强化胰岛素治疗增加死亡率，与4.5-6mmol/dl的目标血糖水平相比 ，10mmol/dl及以下的血糖水平能降低死亡率 On the basis of our results, we do not recommend use of the lower target in critically ill adults. 推建目标血糖水平为10mmol/dl及以下,several

29、 questions?,为什么时隔仅仅8年，同样的强化血糖控制竟然有完全颠倒的两种结果？ Van den berge的鲁纹研究 和NICE SUGAR研究之间结论为何出现如此显著差异 NICE-SUGAR研究同样对监护医学领域始终在热捧的Bundle策略的推广和国际指南的制定有何影响？,2009,2008,2001,Intensive insulin therapy,SSC guidelines,NICE SUGAR,相关述评 （一）,March 26, 2009 美国内分泌协会,Finally, the rush to deploy difficult and resource-intens

30、ive protocols in ICUs may be premature until there is a better understanding of the reasons that the NICE-SUGAR results differ so markedly from those of an earlier study by Van den Berghe et al. 在明确原因之前，贸然推动复杂且消耗资源的规章指南还为时尚早 We believe physicians should individually tailor their approach to glycemic

31、 control in their ICU patients, perhaps targeting glucose values between 144-180 mg/dl, until we better understand the reasons for these somewhat counterintuitive findings 在未阐明各项强化血糖控制研究结论为何出现如此显著差异之前，危重病血糖控制的目标还是订在144-180 mg/dl是合适,The Endocrine Society Statement to Providers on the Report Published

32、 in the New England Journal of Medicine on NICE-SUGAR March 26, 2009,mayo clinic proceedings 梅奥临床学报,澳大利亚和日本学者的联合述评 鲁纹大学van den berge第一次强化血糖控制研究存在的问题，例如非双盲;主要病种限于心外科患者;转入ICU后每日静脉糖量200-300g以及24小时内即开始PNEN或混合喂养等非常规治疗，对照组术后病死率是澳大利亚的2倍；病死率如果未经校准可下降42%，这是任何治疗都无法达到的，低血糖的风险等 At that time, we chose not to hig

33、hlight even more sources of concern, such as the intrinsic limitations of single-center studies, which make them unsuitable for level I evidence 单中心的研究提供不了一级证据,What Is a NICE-SUGAR for Patients in the Intensive Care Unit?,相关述评 （二） A NUMBER OF SERIOUS LIMITATIONS,否定了强化胰岛素治疗，肯定NICE-SUGAR trial,the sec

34、ond largest randomized study sample (to our knowledge) in the history of critical care medicine, it would clearly provide level I evidence to guide clinicians in their decision making at the bedside NICE SUGAR研究为临床医生的工作提供了一级证据 This detrimental intensive insulin therapy (IIT) mortality effect in the

35、NICE-SUGAR trial occurred in all subgroups, including surgical patients. As such, when considering a diverse population of ICU patients, the IIT express has surely come to its last stop（强化血糖可以休矣！）.,Several questions will be asked,Why did the NICE-SUGAR trial show such a different outcome from the fi

36、rst Leuven study? Why and how did IIT cause increased mortality? How should we treat hyperglycemia in patients in the ICU? 问题是为何研究结论大相径庭，强化血糖又是如何增加病死率的，今后我们如何治疗ICU内的高血糖？ We think it is important to emphasize that the findings of NICE-SUGAR do not justify neglecting glycemic control 不过需要强调不要因为NICE-SU

37、GAR今后就忽视血糖的控制,What Is a NICE-SUGAR for Patients in the Intensive Care Unit?,Do not treat hyperglycemia unless the glucose level increases higher than 180 mg/dL; when you do treat hyperglycemia, aim for a target blood glucose concentration between 144 and 180 mg/dL. Until a study can provide level I

38、evidence that a better approach exists, this should remain the standard of care 重症患者血糖不高于180 mg/dl可不处理，如果一定要控制血糖，目标血糖应该是144-180 mg/dl，除非之后出现更好的1级证据，否则NICE-SUGAR研究就是标准方案,What Is a NICE-SUGAR for Patients in the Intensive Care Unit?,相关述评 （三） Annals of Internal Medicine 内科学纪事,Glucose Control in the Int

39、ensive Care Unit: A Roller Coaster Ride or a Swinging Pendulum?” NICE-SUGAR：过山车还是小钟摆?,2 June 2009 | Volume 150 Issue 11 | Pages 809-811,Practice guidelines for some conditions seem to be on a roller coaster. The guidelines recommend a practice, but within a few years the evidence changes, and then t

40、hey recommend against the practice. 临床的指南非常像云霄飞车，一会可以，一会不可以 In fact, the evidence base does change rapidly. A study of 100 quantitative systematic reviews showed that the evidence changed enough to alter the conclusions of a review at a median 5.7 years after its publication 证据的变化非常快。一篇文章经过5.7年之后结论就

41、会大相径庭 However, the evidence base for glucose control in ICU patients better resembles a swinging pendulum rather than a roller coaster. ICU的血糖控制不像云霄飞车，而更像左摇右晃的钟摆,2 June 2009 | Volume 150 Issue 11 | Pages 809-811,2001年的比利时的研究，研究获得的收益连安内分泌专家都非常吃惊，这个时侯钟摆的位置不说大家也知道 不少研究都没有能再次证明鲁汶的结论,钟摆的位置现在开始向中间偏了 NICE-

42、SUGAR把钟摆推向了强化血糖控制的反面 I believe that we must avoid tight control protocols that cause increased rates of hypoglycemia. 一定要避免可能增加低血糖风险的强化血糖控制方案,2 June 2009 | Volume 150 Issue 11 | Pages 809-811,sweet spot,作者认为可能存在一个“sweet spot位点”，既能够避免低血糖的危害又能够严重代谢障碍导致的不良后果。尽管目前还没有证据能够证明它的存在,2 June 2009 | Volume 150 I

43、ssue 11 | Pages 809-811,小结,好的ICU医生对指南的接受应该是辨证的 血糖控制可以总结为过去是“七（mmol/L）上八（mmol/L）下”，现在是“八九不离十（mmol/L） 低血糖危害更大，避免低血糖的发生,血糖监测和血糖控制,常规测纸片法 化验室用血清法 监测血糖值 初期频繁监测血糖(每3060min) 血糖稳定后定期监测(每4h) 控制血糖的方法： 持续输注胰岛素和葡萄糖,微量泵持续泵入普通胰岛素,基础治疗 生理盐水50 ml+胰岛素50 u，其含量为1U /ml，使用微量泵泵入,泵入速率1 ml/h即1U /h 调整方法 入院时同时送检实验室血糖及纸片法血糖测定，明确血糖增高，启动治疗 肠外营养 补充胰岛素按常规剂量 （1：46），再根据患者血糖水平调整比例,