ICU患者血糖的控制精品課件

1、ICU患者血糖的監(jiān)測(cè)與管理,血糖的來(lái)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,非糖物質(zhì),食物糖,消化吸收,分解,糖異生,氧化分解,糖原合成,磷酸戊糖途徑等,脂類，氨基酸代謝,血糖水平的調(diào)節(jié),升糖激素： 胰高血糖素，腎上腺皮質(zhì)激素，腎上腺髓質(zhì)激素，生長(zhǎng)激素，甲狀腺素，性激素，,降糖激素： 胰島素(體內(nèi)唯一降低血糖的激素),胰島素與血糖,胰腺胰島細(xì)胞分泌 對(duì)糖代謝的調(diào)節(jié)：促進(jìn)組織細(xì)胞對(duì)葡萄糖的攝取和利用；加速葡萄糖合成為糖原，儲(chǔ)存于肝和肌肉；抑制糖異生；促進(jìn)葡萄糖轉(zhuǎn)變?yōu)橹舅?，?chǔ)存于脂肪組織,血糖水平異常,糖代謝障礙血糖水平紊亂 一高血糖 糖尿

2、?。簍ype1，type 2，特異型糖尿病， 妊娠糖尿病 應(yīng)激狀態(tài)下的高血糖狀態(tài) 二低血糖,應(yīng)激狀態(tài)下發(fā)生高血糖的原因,反向調(diào)節(jié)激素產(chǎn)生增加,誘發(fā)炎癥反應(yīng)的細(xì)胞因子產(chǎn)生 增多，誘發(fā)胰島素抵抗,外源性因素的作用進(jìn)一步促使高血 糖的發(fā)生（激素，含糖液體）,高血糖,高血糖的危害,患者血糖異常,應(yīng)激狀態(tài)下的高血糖狀態(tài)合并胰島素抵抗 分解代謝加速,糖異生作用加強(qiáng) 激活機(jī)體神經(jīng)內(nèi)分泌系統(tǒng) 致使代謝激素(兒茶酚胺、皮質(zhì)醇、胰高血糖素、生長(zhǎng)激素) 分泌異常 細(xì)胞因子大量釋放和胰島素抵抗,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. 超過(guò)90 的危重病人會(huì)發(fā)生高血糖，并且會(huì)增加幾乎所有亞組ICU患者的發(fā)病率和死亡率,最佳目標(biāo)血糖水平？,是否血糖水平在正常范圍內(nèi)就能降低死亡率？ 什么樣的血糖水平可使ICU患者獲益最大？,血糖控制史上的“里程碑”,2009年,2008年,2001年,NICE SUGAR研究,Surviving Sepsis Campaign,強(qiáng)

4、化血糖控制,血糖控制-強(qiáng)化胰島素治療,前瞻性隨機(jī)對(duì)照試驗(yàn) 外科ICU機(jī)械通氣成人患者1548例 隨機(jī)分為： 強(qiáng)化胰島素治療組 傳統(tǒng)治療組,強(qiáng)化胰島素治療組 維持血糖80110 mg/dL (4.46.1 mmol/L) 傳統(tǒng)治療組 血糖高于215mg/dL(12 mmol/L)輸注胰島素 維持在180200mg/dL(1011mmol/L) .,Intensive insulin therapy in the critically ill patients (危重患者的強(qiáng)化胰島素治療) Van den Berghe G, et al.N Engl J Med 2001; 345: 135913

5、67.,血糖控制-強(qiáng)化胰島素治療,血糖控制-強(qiáng)化胰島素治療,Van den Berghe G, et al: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345: 13591367.,入住后天數(shù) 入院后天數(shù),住院生存率,ICU生存率,血糖控制 -強(qiáng)化胰島素治療,隨后分析表明，盡管將血糖控制在80110 mg/dL (4.46.1 mmol/L)最佳 但是與高血糖比較，目標(biāo)為血糖 150 mg/dL (8.3 mmol/L)也能改善預(yù)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 無(wú)論有無(wú)糖尿病病史，應(yīng)用胰島素將血糖水平控制在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) 我們建議，初步穩(wěn)定后，發(fā)生高血糖的嚴(yán)重膿毒癥的ICU患者應(yīng)接受靜脈胰島素治療來(lái)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) 我們建議使用有效的方案來(lái)調(diào)整胰島素劑量，目標(biāo)血糖水平為 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) 我們建議，所有接受靜脈注射胰島素患者應(yīng)接受葡萄糖為熱量來(lái)源，并且每1-2小時(shí)監(jiān)測(cè)血糖值，直到血糖水平和胰島素輸注率穩(wěn)定后每4小時(shí)監(jiān)測(cè)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) 由手指血糖測(cè)得的低血糖水平應(yīng)持謹(jǐn)慎態(tài)度，因?yàn)檫@種測(cè)量獲得的數(shù)值可能高于動(dòng)脈血或血清值(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患者的生命嗎？,發(fā)表在新英格蘭和HCAMJ雜志上研究的里程碑,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 大樣本，隨機(jī)，對(duì)照試驗(yàn) 42家醫(yī)院的外科和內(nèi)科成人ICU患者，38學(xué)院的三級(jí)保健醫(yī)院，4個(gè)社區(qū)醫(yī)院 四個(gè)國(guó)家和兩個(gè)大洲 6104例隨機(jī)分成2組，強(qiáng)化胰島素治療組3054例和傳統(tǒng)治療組3050例,NICE SUGAR研究 ：Two target ranges groups,強(qiáng)化胰島素治療組the intensive (i.e., tight) control 目標(biāo)血糖水平81108 mg/dL (4.56.0 mmol/L) 傳統(tǒng)治療組the conventional control 目標(biāo)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. 靜脈注射胰島素控制血糖 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). 在傳統(tǒng)治療組如果血糖水平超過(guò)10.0mmol/L;應(yīng)用胰島素。如果血糖水平低于8.0mmol/L胰島素用量減少，然后停止,NICE SUGAR研究 ：結(jié)論,經(jīng)過(guò)總計(jì)6030例患者的校驗(yàn)，強(qiáng)化血糖控制在81-108 mg/dl者的所有主要或次要考察指標(biāo)都顯著差于常規(guī)治療組（血糖述評(píng)180 mg/dl

22、） 強(qiáng)化血糖控制組90天病死率明顯升高 (27.5% vs. 24.9%, p = 0.02， 根據(jù)危險(xiǎn)因素進(jìn)行校正后病死率仍有顯著差異；強(qiáng)化血糖控制組存活時(shí)間縮短 (HR 1.11, 95%CI 1.01 1.23, p = 0.04，強(qiáng)化血糖控制組死于心血管病因的比例更高) ；強(qiáng)化血糖控制組發(fā)生嚴(yán)重低血糖的患者比例明顯升高 (6.8% vs. 0.5%, OR 14.7, 95%CI 9.0 25.9, p 0.001)；同時(shí)，強(qiáng)化血糖控制組在 90天內(nèi)ICU住院日及總住院日；新發(fā)單一或多器官功能衰竭患者比例；機(jī)械通氣時(shí)間，腎臟替代時(shí)間，血培養(yǎng)陽(yáng)性率和輸血比例等諸多方面也沒(méi)有顯示出和常規(guī)治

23、療組之間的差異。,死亡率和生存時(shí)間,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 隨機(jī)分組后90天， 強(qiáng)化胰島素治療組3010例中的829例（ 27.5 ）死亡，而傳統(tǒng)治療組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 平均生存時(shí)間強(qiáng)化胰島素治療組低于傳統(tǒng)治療組,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天存活率強(qiáng)化胰島素組高于傳統(tǒng)治療組,ICU留住時(shí)間,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天的研究期間，2組ICU平均留住時(shí)間沒(méi)有顯著差異,器官功能衰竭，機(jī)械通氣時(shí)間和腎臟替代療法,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) 新發(fā)生的單個(gè)或多器官功能衰竭，2組相似 There was no significant difference between the two groups in the numbers of days of mechanical ventilation and renal replacement therapy 機(jī)械通氣時(shí)間和腎臟替代療法沒(méi)有顯著差異,subgroup analyses,With respect to 90-day mortality, subgroup

27、analyses suggested no significant difference 90天死亡率亞組間沒(méi)有顯著差異,最佳目標(biāo)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). 這次大樣本國(guó)際隨機(jī)實(shí)驗(yàn)顯示：在ICU患者強(qiáng)化胰島素治療增加死亡率，與4.5-6mmol/dl的目標(biāo)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. 推建目標(biāo)血糖水平為10mmol/dl及以下,several

29、 questions?,為什么時(shí)隔僅僅8年，同樣的強(qiáng)化血糖控制竟然有完全顛倒的兩種結(jié)果？ Van den berge的魯紋研究 和NICE SUGAR研究之間結(jié)論為何出現(xiàn)如此顯著差異 NICE-SUGAR研究同樣對(duì)監(jiān)護(hù)醫(yī)學(xué)領(lǐng)域始終在熱捧的Bundle策略的推廣和國(guó)際指南的制定有何影響？,2009,2008,2001,Intensive insulin therapy,SSC guidelines,NICE SUGAR,相關(guān)述評(píng) （一）,March 26, 2009 美國(guó)內(nèi)分泌協(xié)會(huì),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. 在明確原因之前，貿(mào)然推動(dòng)復(fù)雜且消耗資源的規(guī)章指南還為時(shí)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 在未闡明各項(xiàng)強(qiáng)化血糖控制研究結(jié)論為何出現(xiàn)如此顯著差異之前，危重病血糖控制的目標(biāo)還是訂在144-180 mg/dl是合適,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 梅奧臨床學(xué)報(bào),澳大利亞和日本學(xué)者的聯(lián)合述評(píng) 魯紋大學(xué)van den berge第一次強(qiáng)化血糖控制研究存在的問(wèn)題，例如非雙盲;主要病種限于心外科患者;轉(zhuǎn)入ICU后每日靜脈糖量200-300g以及24小時(shí)內(nèi)即開(kāi)始PNEN或混合喂養(yǎng)等非常規(guī)治療，對(duì)照組術(shù)后病死率是澳大利亞的2倍；病死率如果未經(jīng)校準(zhǔn)可下降42%，這是任何治療都無(wú)法達(dá)到的，低血糖的風(fēng)險(xiǎn)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 單中心的研究提供不了一級(jí)證據(jù),What Is a NICE-SUGAR for Patients in the Intensive Care Unit?,相關(guān)述評(píng) （二） A NUMBER OF SERIOUS LIMITATIONS,否定了強(qiáng)化胰島素治療，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研究為臨床醫(yī)生的工作提供了一級(jí)證據(jù) 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（強(qiáng)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? 問(wèn)題是為何研究結(jié)論大相徑庭，強(qiáng)化血糖又是如何增加病死率的，今后我們?nèi)绾沃委烮CU內(nèi)的高血糖？ We think it is important to emphasize that the findings of NICE-SUGAR do not justify neglecting glycemic control 不過(guò)需要強(qiáng)調(diào)不要因?yàn)镹ICE-SU

37、GAR今后就忽視血糖的控制,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 重癥患者血糖不高于180 mg/dl可不處理，如果一定要控制血糖，目標(biāo)血糖應(yīng)該是144-180 mg/dl，除非之后出現(xiàn)更好的1級(jí)證據(jù)，否則NICE-SUGAR研究就是標(biāo)準(zhǔn)方案,What Is a NICE-SUGAR for Patients in the Intensive Care Unit?,相關(guān)述評(píng) （三） Annals of Internal Medicine 內(nèi)科學(xué)紀(jì)事,Glucose Control in the Int

39、ensive Care Unit: A Roller Coaster Ride or a Swinging Pendulum?” NICE-SUGAR：過(guò)山車還是小鐘擺?,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. 臨床的指南非常像云霄飛車，一會(huì)可以，一會(huì)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 證據(jù)的變化非常快。一篇文章經(jīng)過(guò)5.7年之后結(jié)論就

41、會(huì)大相徑庭 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飛車，而更像左搖右晃的鐘擺,2 June 2009 | Volume 150 Issue 11 | Pages 809-811,2001年的比利時(shí)的研究，研究獲得的收益連安內(nèi)分泌專家都非常吃驚，這個(gè)時(shí)侯鐘擺的位置不說(shuō)大家也知道 不少研究都沒(méi)有能再次證明魯汶的結(jié)論,鐘擺的位置現(xiàn)在開(kāi)始向中間偏了 NICE-

42、SUGAR把鐘擺推向了強(qiáng)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風(fēng)險(xiǎn)的強(qiáng)化血糖控制方案,2 June 2009 | Volume 150 Issue 11 | Pages 809-811,sweet spot,作者認(rèn)為可能存在一個(gè)“sweet spot位點(diǎn)”，既能夠避免低血糖的危害又能夠嚴(yán)重代謝障礙導(dǎo)致的不良后果。盡管目前還沒(méi)有證據(jù)能夠證明它的存在,2 June 2009 | Volume 150 I

43、ssue 11 | Pages 809-811,小結(jié),好的ICU醫(yī)生對(duì)指南的接受應(yīng)該是辨證的 血糖控制可以總結(jié)為過(guò)去是“七（mmol/L）上八（mmol/L）下”，現(xiàn)在是“八九不離十（mmol/L） 低血糖危害更大，避免低血糖的發(fā)生,血糖監(jiān)測(cè)和血糖控制,常規(guī)測(cè)紙片法 化驗(yàn)室用血清法 監(jiān)測(cè)血糖值 初期頻繁監(jiān)測(cè)血糖(每3060min) 血糖穩(wěn)定后定期監(jiān)測(cè)(每4h) 控制血糖的方法： 持續(xù)輸注胰島素和葡萄糖,微量泵持續(xù)泵入普通胰島素,基礎(chǔ)治療 生理鹽水50 ml+胰島素50 u，其含量為1U /ml，使用微量泵泵入,泵入速率1 ml/h即1U /h 調(diào)整方法 入院時(shí)同時(shí)送檢實(shí)驗(yàn)室血糖及紙片法血糖測(cè)定，明確血糖增高，啟動(dòng)治療 腸外營(yíng)養(yǎng) 補(bǔ)充胰島素按常規(guī)劑量 （1：46），再根據(jù)患者血糖水平調(diào)整比例,