1、ICU患者血糖的監(jiān)測與管理中南醫(yī)院 ICU 李璐2021/10/23 星期六1血糖的來源和去路血糖3.89 6.11CO2+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2021/10/23 星期六2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) 2021/10/23 星期六3胰島素與血糖胰腺胰島細(xì)胞分泌對糖代謝的調(diào)節(jié)：促進(jìn)組織細(xì)胞對葡萄糖的攝取和利用；加速葡萄糖合成為糖原，儲存于肝和肌肉；抑制糖異生；促進(jìn)葡萄糖轉(zhuǎn)變?yōu)橹舅幔?/p>

2、儲存于脂肪組織2021/10/23 星期六4血糖水平異常糖代謝障礙血糖水平紊亂一高血糖糖尿病：type1，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2021/10/23 星期六5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2021/10/23 星期六6高血糖的危害降低免疫功能和增加感染性并發(fā)癥，成為獨(dú)立因素影響危重癥預(yù)后長期慢性高血糖所致心腦腎血管損害，視網(wǎng)膜病變和神經(jīng)病變減慢傷口愈合高血糖毒性2021/10/23 星期六7患者血糖異常應(yīng)激狀態(tài)下的高血糖狀

3、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、生長激素) 分泌異常細(xì)胞因子大量釋放和胰島素抵抗2021/10/23 星期六8ICU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. 超過90 的危重病

4、人會發(fā)生高血糖，并且會增加幾乎所有亞組ICU患者的發(fā)病率和死亡率 2021/10/23 星期六9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？2021/10/23 星期六10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)化血糖控制2021/10/23 星期六11血糖控制-強(qiáng)化胰島素治療前瞻性隨機(jī)對照試驗(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

5、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: 13591367.2021/10/23 星期六12血糖控制-強(qiáng)化胰島素治療平均跟蹤23天結(jié)局強(qiáng)化胰島素 傳統(tǒng)治療ICU死亡 5% 8%住院死亡 7%11%ICU留住5天以上11%16%機(jī)械通氣14天以上 8%12%需血濾/透析腎衰 5% 8%血行感染

6、4% 8%危重病多發(fā)性神經(jīng)病29%52%2021/10/23 星期六13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2021/10/23 星期六14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

7、改善預(yù)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無論有無糖尿病病史，應(yīng)用胰島素將血糖水平控制在110

8、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: 13591367.2021/10/23 星期六152008Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock1. We recommend that, following initial stab

9、ilization, 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 recomm

10、end 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

11、 point-of-care testing of capillary blood be interpreted with caution, as such measurements may overestimate arterial blood or plasma glucose values (Grade 1B).2021/10/23 星期六162008Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock1.We recommend that,

12、 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降低血糖水平 (Grade 1B)2021/10/23 星期六172.We suggest use of a validated protocol for insulin

13、 dose adjustments and targeting glucose levels to the 150 mg/dl range (8.3mmol/L) (Grade 2C)我們建議使用有效的方案來調(diào)整胰島素劑量，目標(biāo)血糖水平為 150 mg/dl (8.3mmol/L) (Grade 2C)2008Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock2021/10/23 星期六183.We recommend that all pati

14、ents 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源，并且每1-2小時監(jiān)測血糖值，直到血糖水平和胰島素輸注率穩(wěn)定后每4小時監(jiān)測血糖值(G

15、rade 1C)2008Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock2021/10/23 星期六194. 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 b

16、lood or plasma glucose values (Grade 1B)由手指血糖測得的低血糖水平應(yīng)持謹(jǐn)慎態(tài)度，因?yàn)檫@種測量獲得的數(shù)值可能高于動脈血或血清值(Grade 1B)2008Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock2021/10/23 星期六20Can controlling blood sugar levels in the ICU save your life? Tue Mar 24, 2009Landmark s

17、tudies 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

18、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患者的生命嗎？發(fā)表在新英

19、格蘭和HCAMJ雜志上研究的里程碑2021/10/23 星期六21NICE 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 hospitalsInvolving 42 hospitals from four countries and t

20、wo continentsOf the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control 大樣本，隨機(jī)，對照試驗(yàn)42家醫(yī)院的外科和內(nèi)科成人ICU患者，38學(xué)院的三級保健醫(yī)院，4個社區(qū)醫(yī)院四個國家和兩個大洲 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 2021/10/23 星期六22NICE SUGAR研究 ：Two target ranges group

21、s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(10.0mmol/L)及以下2021/10/23 星期六23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

22、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).在傳統(tǒng)治療組如果血糖水平超過10.

23、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2021/10/23 星期六24NICE SUGAR研究 ：結(jié)論經(jīng)過總計(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180 mg/dl） 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

24、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 30 mmol/L，先皮下注射 5 u，再靜脈泵入2021/10/23 星期六47應(yīng)用腸內(nèi)營養(yǎng)的患者以營養(yǎng)泵輸入腸內(nèi)營養(yǎng)液，固定輸入速度血糖偏高患者可選用適合糖尿病患者的營養(yǎng)劑（果糖，如：瑞代）行CRRT的患者CRRT可影響血糖水平選用無糖配方的置換液CRRT時加強(qiáng)血糖檢測，CRRT時每2小時測一次血糖2021/10/23 星期六48恢復(fù)三餐飲食的患者危重期患者不進(jìn)食血糖控制較容易,血糖波動較小而患者恢復(fù)進(jìn)食后要加用三餐胰島素 可以按0. 41. 0 U/ kg 給予胰島素總量40 %5

25、0 %作為胰島素基礎(chǔ)量;或者按0. 2 U/ kg 胰島素作為基礎(chǔ)量余下5060 %按早、中、晚各1/ 3 ,于3 餐前以追加劑量的形式輸入皮下2021/10/23 星期六49Protocol 控制方案Manual ProtocolComputer-based Insulin Infusion Protocolefficient low rate of hypoglycemic episodes2021/10/23 星期六502021/10/23 星期六51胰島素輸入方案：血糖目標(biāo)80150 mg/dL（4.48.3mmol/dl）起始血糖濃度100-150 mg/dL（ 4.48.3mmol

26、/dl ）1U/h151-200 mg/dL （ 8.311mmol/dl ）2U/h201-250 mg/dL （ 1113.7mmol/dl ）2U iv, 然后2U/h251-300 mg/dL （ 13.716.5mmol/dl ）4U iv, 然后2U/h300 mg/dL （ 16.5mmol/dl ）4U iv, 然后4U/h2021/10/23 星期六52*FootnoteSource:Source如果葡萄糖，腸內(nèi)或腸外輸入速度下降（或全腸外營養(yǎng)要換成腸內(nèi)），胰島素輸入速度減半 營養(yǎng)支持的患者當(dāng)治療ARDS等疾病時，可將氫化可的松每日總量持續(xù)靜脈泵入 應(yīng)用皮質(zhì)類固醇的患者繼續(xù)之

27、前的胰島素用法和口服降糖藥物用法按調(diào)整方案調(diào)整胰島素用量，如果血糖6小時仍未達(dá)標(biāo)或速度超過10U/h， 請通知醫(yī)生如果縮血管藥物（腎上腺素，去甲腎上腺素，血管加壓素，.苯腎上腺素， 多巴胺），皮質(zhì)類固醇或者連續(xù)靜脈血液透析停用，將之前泵入速度減半, 并1小時內(nèi)復(fù)測血糖2021/10/23 星期六532021/10/23 星期六54血糖監(jiān)測每12小時然后每24小時檢查血鉀濃度如果血糖5.5則復(fù)查如果血糖27.5mmol/dl或者與臨床情況不符，送實(shí)驗(yàn)室復(fù)查如果臨床狀況顯著改變則恢復(fù)為Q1h（縮血管藥物，CRRT，營養(yǎng)支持，糖皮質(zhì)激素）血糖穩(wěn)定（至少2次測得值達(dá)標(biāo)）前每小時測一次，然后改為Q2h，

28、一旦達(dá)標(biāo)達(dá)12h，減為Q4h2021/10/23 星期六55調(diào)整方案血糖濃度0.13.9 U/h46.9 U/h710 U/h10 U/h5.5時，胰島素減半輸入，Q1h復(fù)測2.73.8停用胰島素，20ml 50%葡萄糖IV，15min復(fù)測血糖，必要時重復(fù)至少1h后再用胰島素，通知醫(yī)生如果沒有營養(yǎng)，可用5%葡萄糖滴注當(dāng)血糖5.5時，胰島素減半輸入，Q1h復(fù)測3.84.4停用胰島素， 1h復(fù)測血糖，若血糖5.5，減半輸入， 1h復(fù)測血糖停用胰島素， 1h復(fù)測血糖，若血糖5.5，減少2U/h輸入， 1h復(fù)測血糖停用胰島素， 1h復(fù)測血糖，若血糖5.5，減少3U/h輸入， 1h復(fù)測血糖停用胰島素， 1h復(fù)測血