1、亞低溫技術(shù)在心肺復(fù)蘇中的應(yīng)用Therapeutic hypothermia in post-resuscitation patients,上海交通大學(xué)醫(yī)學(xué)院附屬瑞金醫(yī)院陸一鳴,提綱,心跳驟停的流行病學(xué)及其預(yù)后亞低溫療法和其作用機(jī)制亞低溫治療心跳驟停病人的循證學(xué)依據(jù)哪一種亞低溫療法最有效?教育、實(shí)施和科研方面的挑戰(zhàn),猝死病人死亡率近70%,,心臟驟停的流行病學(xué),400,000 驟停 / 每年在 U.S.A醫(yī)院,3 / 4

2、門急診,1 / 4 住院患者,出院時(shí)的存活率,1-5% 10-20%,,,,,,,,只有 2%的幸存患者神經(jīng)性功能良好,Mry Ann Peberdy, Joseph P Ornato,,High quality post resuscitation care,Survival rates among those admitted vary from 0 – 60%!,低溫治療

3、的分類,低溫治療作用機(jī)制,傳統(tǒng)認(rèn)為：低溫主要通過降低葡萄糖和氧耗延緩代謝而起到保護(hù)作用,低溫治療作用機(jī)制的新觀念,抗凋亡、Ca2+介導(dǎo)的蛋白水解作用和線粒體損傷穩(wěn)定離子泵和抑制神經(jīng)興奮性級(jí)聯(lián)反應(yīng)抑制免疫和炎癥反應(yīng)抗自由基損傷降低血管滲透性和減輕腦水腫減輕細(xì)胞膜滲透性改變和細(xì)胞內(nèi)酸中毒抑制腦內(nèi)局部溫度升高后的腦損害降低腦代謝,Bladder Temperature in the Normothermia and Hypoth

4、ermia Groups. 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 cooli

5、ng was 24 hours. Only patients with recorded temperatures were included in the analysis.,Cooling End,After 6 months: Rate of death (41%) in the hypothermia is 14% lower than in the normothermia group (39%).,歐洲多中心臨床試驗(yàn)（ H

6、ACA trial),隨機(jī)將275名患者分組為低溫或常溫兩組 降溫時(shí)間：使用體表降溫降到34度耗時(shí)6.5個(gè)小時(shí)結(jié)果： 低體溫 正常體溫好的結(jié)果 55%39% p=0.009死亡率 41%55% p=0.02,每六個(gè)接受治療的患者，有一個(gè)可救活！,,Number needed to treat to achieve good

7、 neurological outcome in one extra patient:,6,Holzer M et al., Crit Care Med 2005; 33:414-8.,澳大利亞的研究,77名患者的隨機(jī)臨床試驗(yàn)使用冰袋冷卻0.9度/小時(shí) 結(jié)果: 低體溫 正常體溫好結(jié)果 49%26% p=0.046死亡率51%68%

8、P=NS,Preliminary evidence in patients with asystole/PEA…,Polderman KH et al. Induced hypothermia improves neurological outcomein asystolic patients with out-of hospital cardiac arrest.Circulation 2003; 108: IV-581 [abs

9、tract 2646],歐洲HART Study - ICY 在心臟驟停的多中心試驗(yàn),心搏停跳后，ICY 導(dǎo)管亞低溫治療。前瞻性的，多中心研究對(duì)心搏停搏患者使用ICY導(dǎo)管進(jìn)行可行性和安全性評(píng)估多中心參加: Henry Ford, Duke, University of Houston歐洲復(fù)蘇理事會(huì)資助 30 多個(gè)中心參加，包括500名患者，結(jié)果在2005年9月阿姆斯特丹會(huì)議上公布。歐洲HACA 調(diào)查者將使用CoolGard 3

10、000和Icy 導(dǎo)管作為金標(biāo)準(zhǔn)降溫療法。,,,,,,Before- and after comparison in 665 out-of hospital cardiac arrest in the Stavanger area (population 300 000) 2001-2003,,,,Before- and after comparison in 665 out-of hospital cardiac arrest in t

11、he Stavanger area (population 300 000) 2001-2003,Cooling Procedure,introduce the cooling device (Icy and CoolGard 3000; Alsius Corp),foley-catheter,24 h,target temperature at 33℃,rewarmed,0.5 ℃ /h,36~37 ℃,,,,,Icy-cathet

12、er,Start up Kit,,,,,,,All patients in the database from August 1991 to November 2004 were screened. For outcome evaluation all patients who were cooled with endovascular cooling during this period were evaluated. For eva

13、luation of cooling rate we restricted the analysis to patients who received endovascular cooling exclusively.,Bladder temperature course. Median, 25th and 75th quartile of bladder temperature after return of spontaneous

14、circulation in patients, who were exclusively cooled with the endovascular cooling device (n=56). Target temperature, 33°C; cooling duration, 24 hours.,95 min 35.3±1.0℃,253 min 33 ℃,24 hr,388 min36 ℃,1.2 ℃ /ho

15、ur,Adverse Event,,Endovascular Cooling (n=62),,Control (n=104),,P,,Complications During and After Endovascular Cooling Compared to Frequency-Matched Controls,,Methods -- Consecutive comatose survivors of cardiac arrest

16、, who were either cooled for 24 hours to 33°C with endovascular cooling or treated with standard postresuscitation therapy, were analyzed. Complication data were obtained by retrospective chart review.Results -- P

17、atients 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, 1.45 to 3.57; P<0.001). After adjustment for baseline imbalances the odds r

18、atio 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

19、to 3.35; P=0.0003; adjusted 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 r

20、ecovery compared with standard treatment in comatose adult survivors of cardiac arrest. Temperature control was effective and safe with this device.,An advisory statement by the Advanced Life Support Task Force of the In

21、ternational Liaison Committee on Resuscitation(ILCOR – includes AHA)(Published in Resuscitation, June 2003 and Circulation, July 2003),對(duì)于無知覺的具有自發(fā)循環(huán)的門急診心臟驟?；颊?，如果出現(xiàn)最初室顫節(jié)律，則應(yīng)該將該患者體溫降到 32-34度達(dá)12-24小時(shí)。像這樣的降溫也對(duì)其它的節(jié)律性疾病或住院的心

22、臟驟?；颊哂幸?。,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

23、. In a select subset of patients who were initially comatose but hemodynamically stable after a witnessed VF arrest of presumed cardiac etiology, active induction of hypothermia was beneficial. Thus, unconscious adult pa

24、tients with ROSC after out-of-hospital cardiac arrest should be cooled to 32℃ to 34 ℃ for 12 to 24 hours when the initial rhythm was VF (Class IIa). Similar therapy may be beneficial for patients with non-VF arrest out o

25、f hospital or for in-hospital arrest (Class IIb)’.,Probably as quickly as possible,Cardiac Arrest,,ROSC,0 1 2 3 4 5 6 7 8,Time,,Intra-arrest Abella, 2004Katz, 2000,,,Soon after ROSCSter

26、z, 1991Kuboyama, 1993,,HACA, 2002,When to start cooling?,,Bernard, 2002,Prehospital and ED cooling? YES!,體表降溫－冰袋,冰袋，通常把它放在患者腹股溝，位于身體體表的位置，腋窩下和頭周圍。護(hù)士要不斷地清理由于冰袋融化而出來的冷凝水和不斷地挪動(dòng)冰袋的位置以防溫度太低造成的局部組織損傷,Bernard et al, Rescuscita

27、tion 2003;56:9-13; Virkkunen et al., Resuscitation 2004; 62:299-302; Rijnsburger Intensive Care Med 2004 30:Suppl 1 abstr 475; Polderman et al. Critical Care Med 2005; 33:2744-51.,Cold fluid infusion?,Three studiesP

28、ost-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 re

29、ach target temp),體表降溫－kcl床,kcl床，這種床用于歐洲的HACA (心臟停搏后的低溫治療）實(shí)驗(yàn)， 將病人放置到帶有拉鏈的袋子中，然后吹入冷氣包圍患者身體，可以想象患者被包圍住的護(hù)理有多困難。,Invasive or non-invasive cooling technique?,New knowledge, new methods and new equipment!,,,亞低溫治療程序：治療的3個(gè)不同階段,,嚴(yán)

30、格控制在32-34度,緩慢，可控的復(fù)溫以免顱內(nèi)壓反彈,,必須能夠完全控制3個(gè)階段,Temperature Profile Using Icy? Catheter (Cooling time: 98 minutes）,,與目標(biāo)溫度一致,,快速降溫,緩慢，可控復(fù)溫階段,HACA 試驗(yàn) vs ALSIUS Icy?,,,,,,,,,,21 (51),18 (65),75 (55),54 (39),Good,18 (44),23 (56),

31、All rhythmsn=41,Icy?,8 (29),20 (71),VF onlyn=28,Icy?,,,,,56 (41),76 (55),Dead,81(59),62 (45),Alive,Hypothermia(低體溫）,Control,,HACA Trialn (%),,,,,,,.28,.02,結(jié)果趨向于使用血管內(nèi)冷卻方法更有效。,6 個(gè)月的結(jié)果,體表降溫和血管腔內(nèi)降溫,體表降溫護(hù)理工作強(qiáng)度大(ice packs/

32、lavage bladder,ngt/cooling blanket)很難維持目標(biāo)溫度-降溫過度 不可控制復(fù)溫 – ICP ( 顱壓）反彈和體溫過高增加寒戰(zhàn)過度的護(hù)理操作（冰墊/降溫毯）對(duì)病情不穩(wěn)定的患者有不良影響血管腔內(nèi)降溫開始治療容易（中心靜脈入路） 不影響患者的護(hù)理工作與體表降溫相比減少寒戰(zhàn)次數(shù)容易快速與患者分離有效地控制降溫后的患者體溫反彈，ICU 患者最多可以使用4天,血管內(nèi)降溫,冰毯,結(jié)果：與表面降溫組相

33、比，血管內(nèi)降溫組：降溫迅速在溫度維持階段，溫度波動(dòng)小(±0.1℃ )復(fù)溫更加迅速,European ICU survey: therapeutic hypothermia use (Boerriger et al, 2006),Around 60% reported use of therapeutic hypothermia65% cooled all comatose survivors10% only witn

34、essed 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 therapeu

35、tic hypothermia in Norway,All patients with ROSC after cardiac arrest who are not following verbal commands!Only witnessed arrestOnly VF/VT and age 18-75 (HACA/Bernard study inclusion criteria)out-of-hospital ventric

36、ular fibrillation★★★ Asystole★★ pulseless electrical activity（PEA）★★,Patient selection,When should mild hypothermia be started? How rapidly should the cooling take place? How long to cool ? 12 hours or 24 hours (NEJ

37、M 2002; 346:549–556 vs. 346:557–563) ?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 ve

38、ntricular fibrillation?Can we differentiate those patients who will benefit from mild hypothermia and those who will not?,Still a lot of questions…,Prognostic indicators,In a meta-analysis of 11 studies involving almost

39、 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 pupillary response at 24 h; no motor response at

40、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 24–72 h. An electroencephalogram after 24–48