ICU患者血糖的控制+09-8-1

nullICU患者血糖的监测与管理ICU患者血糖的监测与管理中南医院 ICU 李璐血糖的来源和去路血糖的来源和去路血糖 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，ＨＣＧ降糖激素： 胰岛素(体内唯一降低血糖的激素) 胰岛素与血糖胰岛素与血糖胰腺胰岛Ｂ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 应激状态下发生高血糖的原因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高血糖的危害ＩＣＵ患者血糖异常ＩＣＵ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 最佳目标血糖水平？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”血糖控制史上的“里程碑”2009年2008年2001年NICE SUGAR研究Surviving Sepsis Campaign强化血糖控制血糖控制--强化胰岛素治疗血糖控制--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80~110 mg/dL (4.4~6.1 mmol/L) 传统治疗组 血糖高于215mg/dL(12 mmol/L)输注胰岛素 维持在180~200mg/dL(10~11mmol/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: 1359–1367. 血糖控制--强化胰岛素治疗血糖控制--强化胰岛素治疗血糖控制--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: 1359–1367. 入住后天数 入院后天数住院生存率 ICU生存率血糖控制 --强化胰岛素治疗血糖控制 --强化胰岛素治疗随后明，尽管将血糖控制在80~110 mg/dL (4.4~6.1 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: 1359–1367. 2008---Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock 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 1–2 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). 2008---Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock 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)2008---Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock 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 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 blood glucose values be monitored every 1–2 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 2008---Surviving Sepsis Campaign: International guidelines for management 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 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? Can controlling blood sugar levels in the ICU save your life? Tue Mar 24, 2009 Landmark 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NICE SUGAR研究 ：Background 背景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 NICE SUGAR研究 ：Two target ranges groupsNICE 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81~108 mg/dL (4.5~6.0 mmol/L) 传统治疗组the conventional control 目标血糖水平180mg/dL(10.0mmol/L)及以下 方法方法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 NICE SUGAR研究 ：结论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 < 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疗组之间的差异。 null死亡率和生存时间死亡率和生存时间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 lower 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). 90天存活率强化胰岛素组高于传统治疗组ICU留住时间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 similar 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nullsubgroup analysessubgroup analysesWith respect to 90-day mortality, subgroup 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 lower 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 questions?several 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 20082001 Intensive insulin therapySSC guidelinesNICE SUGAR相关述评 （一）相关述评 （一）March 26, 2009 美国内分泌协会 Finally, the rush to deploy difficult and resource-intensive protocols in ICU’s 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 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 in the New England Journal of Medicine on NICE-SUGAR March 26, 2009 mayo clinic proceedings 梅奥临床学报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PN\EN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 highlight 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 否定了强化胰岛素治疗，肯定NICE-SUGAR trial the second 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 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 askedSeveral questions will be askedWhy did the NICE-SUGAR trial show such a different outcome from the first 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-SUGAR今后就忽视血糖的控制 What Is a NICE-SUGAR for Patients in the Intensive Care Unit?null 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 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》 相关述评 （三） Annals of Internal Medicine 《内科学纪事》 Glucose Control in the Intensive 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 nullPractice 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 they 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 null2001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-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 spotsweet 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 Issue 11 | Pages 809-811 小结小结好的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 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30~60min) 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 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 （1：4~6），再根据患者血糖水平调整比例血糖控制血糖控制要求在12～24h内使血糖达到控制目标 血糖测定连续3次以上达控制目标,测定频率可改为4h一次 起始剂量4～6U/ h 血糖以每小时4～6mmol/ L 速度下降 如果2 h 血糖不能满意下降, 提示患者对胰岛素敏感性下降, 胰岛素剂量宜加倍至10～12U/ h 若血糖下降速度过快, 则根据情况减少胰岛素的泵入 初始血糖值>30 mmol/L，先皮下注射 5 u，再静脉泵入应用肠内营养的患者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小时测一次血糖恢复三餐饮食的患者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. 4～1. 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50～60 %按早、中、晚各1/ 3 ,于3 餐前以追加剂量的形式输入皮下Protocol 控制方案Protocol 控制方案Manual Protocol Computer-based Insulin Infusion Protocolefficient low rate of hypoglycemic episodesnull胰岛素输入方案： 血糖目标80–150 mg/dL（4.4~8.3mmol/dl）胰岛素输入方案： 血糖目标80–150 mg/dL（4.4~8.3mmol/dl）起始血糖浓度null * 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 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 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null血糖监测血糖监测每12小时然后每24小时检查血钾浓度如果血糖<3.3或在稳定情况下改变>5.5则复查如果血糖>27.5mmol/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调整方案调整方案低血糖低血糖正常　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 神经系统症状 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 临床表现的严重程度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，慢性低血糖病人低血糖的治疗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40～100ml，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nullTHANK YOU !