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1、亚低温技术在心肺复苏中的应用亚低温技术在心肺复苏中的应用Therapeutic hypothermia in post-resuscitation patients上海交通大学医学院附属瑞金医院上海交通大学医学院附属瑞金医院陆一鸣陆一鸣提纲提纲1.心跳骤停的流行病学及其预后2.亚低温疗法和其作用机制3.亚低温治疗心跳骤停病人的循证学依据4.哪一种亚低温疗法最有效?5.教育、实施和科研方面的挑战猝死病人死亡率近猝死病人死亡率近70%350000350000 猝死病人猝死病人猝死病人猝死病人100000100000 尝试做尝试做尝试做尝试做 CPR CPR4000040000 到达医院病人到达医院
2、病人到达医院病人到达医院病人2000020000 活着出医院活着出医院活着出医院活着出医院 1200012000 没有或很少有后遗症没有或很少有后遗症没有或很少有后遗症没有或很少有后遗症心脏骤停的流行病学心脏骤停的流行病学400,000 骤停骤停/每年在医院每年在医院3/4 门急诊门急诊1/4 住院患者住院患者出院时的存活率出院时的存活率 1-5%10-20%只有只有 2%的幸存患者神经性功能良好的幸存患者神经性功能良好Mry Ann Peberdy,Joseph P OrnatoHigh quality High quality post resuscitation care post re
3、suscitation care Survival rates among those admitted vary from 0 60%!Survival rates among those admitted vary from 0 60%!低温治疗的分类低温治疗的分类分类英文名称目标温度轻度低温mild hypothermia3335亚低温亚低温(mild hypothermia)，亚低温状态下，对心脑肺的保护作用与深度低温相似，但无明显不良反应中度低温moderate hypothermia2832深度低温profound hypothermia172728以下低温容易引起低血压和心律失常
4、等并发症，目前较少使用超深度低温ultraprofound hypothermia16低温治疗作用机制低温治疗作用机制传统认为：低温主要通过降低葡萄糖和氧耗延缓代谢而起到保护作用诱导低温条件下体温下降1 脑代谢率下降57 低温治疗作用机制的新观念低温治疗作用机制的新观念抗凋亡、Ca2+介导的蛋白水解作用和线粒体损伤稳定离子泵和抑制神经兴奋性级联反应抑制免疫和炎症反应抗自由基损伤降低血管渗透性和减轻脑水肿减轻细胞膜渗透性改变和细胞内酸中毒抑制脑内局部温度升高后的脑损害降低脑代谢Bladder Temperature in the Normothermia and Hypothermia Grou
5、ps.The T bars indicate the 75th percentile in the normothermia group and the 25th percentile in the hypothermia group.The target temperature in the hypothermia group was 32 to 34,and the duration of cooling was 24 hours.Only patients with recorded temperatures were included in the analysis.Cooling E
6、ndAfter 6 months:75 of the 136(55%)in hypothermia group had better favorable neurologic outcome than normothermia group(39%).After 6 months:Rate of death(41%)in the hypothermia is 14%lower than in the normothermia group(39%).欧洲多中心临床试验（欧洲多中心临床试验（HACA trial)随机将随机将275名患者分组为低温或常温两组名患者分组为低温或常温两组 结果：结果：低体
7、温低体温 正常体温正常体温好的结果好的结果 55%死亡率死亡率 41%每六个接受治疗的患者，每六个接受治疗的患者，有一个可救活！有一个可救活！Number needed to treat to achieve good neurological outcome in one extra patient:6 Holzer M et al.,Crit Care Med 2005;33:414-8.澳大利亚的研究澳大利亚的研究77名患者的随机临床试验名患者的随机临床试验使用冰袋冷却度使用冰袋冷却度/小时小时 结果结果:低体温低体温 正常体温正常体温好结果好结果 49%死亡率死亡率51%68%P=NS
8、Preliminary evidence in patients with asystole/PEAPolderman KH et al.Induced hypothermia improves neurological outcomein asystolic patients with out-of hospital cardiac arrest.Circulation 2003;108:IV-581 abstract 2646欧洲欧洲HART Study-ICY 在心脏骤停的多在心脏骤停的多中心试验中心试验 心搏停跳后，ICY 导管亚低温治疗。前瞻性的，多中心研究对心搏停搏患者使用ICY导
9、管进行可行性和安全性评估多中心参加:Henry Ford,Duke,University of Houston欧洲复苏理事会资助 30 多个中心参加，包括500名患者，结果在2005年9月阿姆斯特丹会议上公布。欧洲HACA 调查者将使用CoolGard 3000和Icy 导管作为金标准降温疗法。Before-and after comparison in 665 out-of hospital cardiac arrest in the Stavanger area(population 300 000)2001-2003Before-and after comparison in 665 o
10、ut-of hospital cardiac arrest in the Stavanger area(population 300 000)2001-2003Cooling Procedure introduce the cooling device(Icy and CoolGard 3000;Alsius Corp)foley-catheter24 htarget temperature at 33 rewarmed0.5 /h3637 Icy-catheterStart up KitAll patients in the database from August 1991 to Nove
11、mber 2004 were screened.For outcome evaluation all patients who were cooled with endovascular cooling during this period were evaluated.For evaluation of cooling rate we restricted the analysis to patients who received endovascular cooling exclusively.Bladder temperature course.Median,25th and 75th
12、quartile of bladder temperature after return of spontaneous circulation in patients,who were exclusively cooled with the endovascular cooling device(n=56).Target temperature,33C;cooling duration,24 hours.95 min 35.31.0 253 min 33 24 hr388 min36 1.2 /hour Adverse Event Endovascular Cooling(n=62)Contr
13、ol(n=104)P Within the first 32 hAtrial fibrillation,n(%)2(3)2(3)0.987Ventricular tachycardia,n(%)14(23)9(14)0.231Ventricular fibrillation,n(%)6(10)6(10)0.977Narrow complex tachycardia,n(%)03(5)0.082Bradycardia,n(%)9(15)2(3)0.025Any Bleeding,n(%)16(26)27(26)0.982 Within the first 7 dPneumonia,n(%)17(
14、27)20(19)0.233Elevation of pancreatic enzymes,n(%)1(2)00.194Sepsis,n(%)00.Acute renal failure,n(%)4(6)4(4)0.448Complications During and After Endovascular Cooling Compared to Frequency-Matched Controls Methods-Consecutive comatose survivors of cardiac arrest,who were either cooled for 24 hours to 33
15、C with endovascular cooling or treated with standard postresuscitation therapy,were analyzed.Complication data were obtained by retrospective chart review.Results-Patients in the endovascular cooling group had 2-fold increased odds of survival(67/97 patients vs 466/941 patients;odds ratio 2.28,95%CI
16、,1.45 to 3.57;P0.001).After adjustment for baseline imbalances the odds ratio was 1.96(95%CI,1.19 to 3.23;P=0.008).In the endovascular cooling group,51/97 patients(53%)survived with favorable neurology as compared with 320/941(34%)in the control group(odds ratio 2.15,95%CI,1.38 to 3.35;P=0.0003;adju
17、sted odds ratio 2.56,1.57 to 4.17).There was no difference in the rate of complications except for bradycardia.Conclusion-Endovascular cooling improved survival and short-term neurological recovery compared with standard treatment in comatose adult survivors of cardiac arrest.Temperature control was
18、 effective and safe with this device.An advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation(ILCOR includes AHA)(Published in Resuscitation,June 2003 and Circulation,July 2003)对于无知觉的具有自发循环的门急诊心脏骤停患者，如果出现最初室颤节律，则应该将该患者体温降到 32-34度达12-24小时。像
19、这样的降温也对其它的节律性疾病或住院的心脏骤停患者有益。ILCOR Recommendations ILCOR Recommendations International Emergency Cardiac Care Guidelines（2005）mild hypothermia may be beneficial to neurologic outcome and is likely to be well tolerated without significant risk of complications.In a select subset of patients who were i
20、nitially comatose but hemodynamically stable after a witnessed VF arrest of presumed cardiac etiology,active induction of hypothermia was beneficial.Thus,unconscious adult patients with ROSC after out-of-hospital cardiac arrest should be cooled to 32 to 34 for 12 to 24 hours when the initial rhythm
21、was VF(Class IIa).Similar therapy may be beneficial for patients with non-VF arrest out of hospital or for in-hospital arrest(Class IIb).Probably as quickly as possibleCardiac ArrestROSC0 1 2 3 4 5 6 7 8TimeIntra-arrest Abella,2004Katz,2000Soon after ROSCSterz,1991Kuboyama,1993HACA,2002When to start
22、 cooling?Bernard,2002Prehospital and ED cooling?YES!体表降温冰袋体表降温冰袋冰袋，通常把它放在患者腹股沟，位于身体体表的位置，腋窝下和头周围。护士要不断地清理由于冰袋融化而出来的冷凝水和不断地挪动冰袋的位置以防温度太低造成的局部组织损伤Bernard et al,Rescuscitation 2003;56:9-13;Virkkunen et al.,Resuscitation 2004;62:299-302;Rijnsburger Intensive Care Med 2004 30:Suppl 1 abstr 475;Polderman
23、et al.Critical Care Med 2005;33:2744-51.Cold fluid infusion?Three studiesPost-ROSC patientsRefrigerated Ringers lactate(40C),saline or colloids to induce hypothermiaAverage volume 1500-3000 ml within 30-60 minHemodynamic improvement and no lung problemsSafe and effective(30-60 min to reach target te
24、mp)体表降温体表降温kcl床床kcl床，这种床用于欧洲的HACA(心脏停搏后的低温治疗）实验，将病人放置到带有拉链的袋子中，然后吹入冷气包围患者身体，可以想象患者被包围住的护理有多困难。Invasive or non-invasive cooling technique?New knowledge,new methods and new equipment!亚低温治疗程序：治疗的亚低温治疗程序：治疗的3个不同阶段个不同阶段快速冷却阶段快速冷却阶段Crash Cool Phase最大化冷却率最大化冷却率 Maximum Cooling Rate37C33C复温阶段复温阶段Rewarm Phas
25、e维持阶段维持阶段严格控制在严格控制在32-34度度缓慢，可控的复缓慢，可控的复温以免颅内压反温以免颅内压反弹弹 必须能够完全控制必须能够完全控制3个阶段个阶段Temperature Profile Using Icy Catheter(Cooling time:98 minutes）与目标温度一致快速降温缓慢，可控复温阶段HACA 试验试验 vs ALSIUS Icy 21(51)18(65)75(55)54(39)Good18(44)23(56)All rhythmsn=41Icy8(29)20(71)VF onlyn=28Icy56(41)76(55)Dead81(59)62(45)Al
26、iveHypothermia(低体温）ControlHACA Trialn(%).28.02 结果趋向于使用血管内冷却方法更有效。结果趋向于使用血管内冷却方法更有效。6 个月的结果个月的结果体表降温和血管腔内降温体表降温和血管腔内降温体表降温体表降温护理工作强度大(ice packs/lavage bladder,ngt/cooling blanket)很难维持目标温度-降温过度 不可控制复温 ICP(颅压）反弹和体温过高增加寒战过度的护理操作（冰垫/降温毯）对病情不稳定的患者有不良影响血管腔内降温血管腔内降温开始治疗容易（中心静脉入路）不影响患者的护理工作与体表降温相比减少寒战次数容易快速与
27、患者分离有效地控制降温后的患者体温反弹，ICU 患者最多可以使用4天血管内降温血管内降温冰毯冰毯结果：结果：与表面降温组相比，血管内降温组：与表面降温组相比，血管内降温组：降温迅速降温迅速在温度维持阶段，温度波动小在温度维持阶段，温度波动小()复温更加迅速复温更加迅速European ICU survey:therapeutic hypothermia use(Boerriger et al,2006)Around 60%reported use of therapeutic hypothermia65%cooled all comatose survivors10%only witnesse
28、d arrest10%only VF/VTReasons given for not using TH:lack of science(5%)and fear of side-effects(2%)lack of consensus(10%)lack of equipment(25%)A”COOL”SUCCESS STORY:rapid implementation of therapeutic hypothermia in NorwayAll patients with ROSC after cardiac arrest who are not following verbal comman
29、ds!Only witnessed arrestOnly VF/VT and age 18-75(HACA/Bernard study inclusion criteria)out-of-hospital ventricular fibrillation Asystole pulseless electrical activity（PEA）Patient selectionWhen should mild hypothermia be started?How rapidly should the cooling take place?How long to cool?12 hours or 2
30、4 hours(NEJM 2002;346:549556 vs.346:557563)?Target temperature?33 degrees or 35 degrees Celsius?How rapidly should warming take place?Is therapeutic hypothermia efficacious for patients with initial rhythms other than ventricular fibrillation?Can we differentiate those patients who will benefit from
31、 mild hypothermia and those who will not?Still a lot of questionsPrognostic indicators In a meta-analysis of 11 studies involving almost 2000 patients in cardiac arrest,there were no immediate clinical signs to predict neurologic outcome.The best clinical signs:absent corneal reflexes at 24 h;absent
32、 pupillary response at 24 h;no motor response at 24 h;and no motor response at 72 h.The estimate of poor outcome for comatose patients following arrest was 77%which increased to 97%with negative clinical indicators at 2472 h.An electroencephalogram after 2448 h of care may also be a useful prognostic guide.