腦復(fù)蘇臨床研究進(jìn)展

岑穎欣 張思森

·綜述·

腦復(fù)蘇臨床研究進(jìn)展

岑穎欣 張思森

心臟驟停是指心臟射血功能突然終止[1],主要臨床表現(xiàn)為患者突然意識喪失,不能觸及大動脈搏動,以及聽診心音消失,伴或不伴有自主呼吸停止,并導(dǎo)致全身多臟器及組織器官因缺血、缺氧而發(fā)生衰竭并最終死亡。心臟驟停是全世界成人死亡的主因之一,每年罹患數(shù)百萬人。及時有效的心肺復(fù)蘇是其惟一的救治措施,但盡管心肺復(fù)蘇技術(shù)在不斷進(jìn)步,心臟驟?；颊叱鲈捍婊盥室廊缓艿?發(fā)達(dá)國家出院存活率不到10%,我國僅有1.3%[2-3]。其中神經(jīng)系統(tǒng)損傷是其主要致死和致殘的主因,即使復(fù)蘇成功也有很大一部分人會造成永久性腦損傷[4-7]。大腦作為人體的司令部,一旦損傷,便難以恢復(fù),且對生活質(zhì)量大打折扣,由此可見腦復(fù)蘇的重要性。

心臟驟停導(dǎo)致腦損傷的機制復(fù)雜,現(xiàn)在普遍認(rèn)為是心臟驟停導(dǎo)致大腦缺血缺氧從而導(dǎo)致腦損傷,自主循環(huán)恢復(fù)后再灌注導(dǎo)致大腦二次損傷,海馬、皮質(zhì)、小腦、丘腦等易損區(qū)細(xì)胞凋亡的出現(xiàn)及加劇是導(dǎo)致呼吸循環(huán)衰竭、細(xì)胞代謝障礙、腦水腫、顱內(nèi)壓增高等病理生理性改變風(fēng)險上升的關(guān)鍵因素[8]。由此,各學(xué)者提出了種種腦復(fù)蘇的治療方法。以下將對腦復(fù)蘇的研究現(xiàn)狀進(jìn)行論述。

一、亞低溫治療

亞低溫治療在臨床上又稱冬眠療法或人工冬眠,是用藥物及物理方法使患者體溫降低,降低腦細(xì)胞代謝用氧需求,以達(dá)到治療的目的。國際上按體溫降低程度一般分為輕度低溫33℃～35℃,中度低溫 28℃～32℃,深度低溫17℃～27℃,輕中度低溫統(tǒng)稱為亞低溫。

20世紀(jì)50年代低溫治療(28℃～35℃)被應(yīng)用于心臟手術(shù)和心臟驟?；謴?fù)自主循環(huán)的患者,可減少腦損傷發(fā)生[9],但因發(fā)生嚴(yán)重不良反應(yīng)(如心律失常),其應(yīng)用受到限制。1987年Busto等[10]首次提出全身低溫(33℃～35℃)的方法具有腦保護(hù)作用。20世紀(jì)90年代中后期,以中國學(xué)者江基堯教授為代表的研究人員將28℃～35℃的輕中度低溫定義為亞低溫,并發(fā)現(xiàn)亞低溫對實驗性缺血和實驗性顱腦外傷具有顯著的治療作用[11-12]。在過去十多年間,基礎(chǔ)研究和臨床研究都表明復(fù)蘇后積極降低血液溫度到32℃～34℃可以提高神經(jīng)功能的恢復(fù)[13-15]。近期研究也指出，早期應(yīng)用亞低溫治療和快速達(dá)到目標(biāo)體溫是提高神經(jīng)功能預(yù)后的關(guān)鍵[13-16]。美國心臟學(xué)會和歐洲復(fù)蘇協(xié)會最新指南建議:院外心臟驟?；謴?fù)自主循環(huán)的昏迷成年患者,當(dāng)初始心律是室顫時,應(yīng)降低體溫到32℃～34℃,且持續(xù)12～24 h[17-18]。

隨著研究的不斷深入,學(xué)者們開始探究亞低溫治療的機制。直到現(xiàn)在,亞低溫治療機制仍然不太明確,大多學(xué)者認(rèn)為其與降低腦的代謝率、抑制腦組織細(xì)胞凋亡、減輕腦水腫、抑制內(nèi)源性損傷因子釋放、減輕再灌注后炎癥反應(yīng)有關(guān)[19]。

隨著亞低溫治療的應(yīng)用,各種并發(fā)癥相繼出現(xiàn),如:延長的凝血時間、寒戰(zhàn)、過冷、肺部感染、免疫抑制、藥物代謝減慢等[20-22]。學(xué)者們開始改進(jìn)亞低溫治療。Sen Ye等[23]通過大鼠實驗提出持續(xù)較短時間比長時間維持低體溫能得到更好的神經(jīng)系統(tǒng)預(yù)后及減少并發(fā)癥;Benjamin等[24]提出快速達(dá)到目標(biāo)溫度比延遲行亞低溫治療腦損傷預(yù)后更好。另外相對于傳統(tǒng)的低溫誘導(dǎo)技術(shù):降溫毯、冰袋、冰帽等,Kim等[25]提出院外開始快速輸注4℃等滲鹽水能在達(dá)到醫(yī)院前有效降溫,且不增加對血壓、心率方面的副作用,不增加肺水腫的發(fā)生率。廖曉星等[26-27]研究表明自發(fā)循環(huán)恢復(fù)(restoration of spontaneous circulation,ROSC)后將4℃低溫液體經(jīng)腹腔灌注,以類似于腹膜透析的方式,可快速誘導(dǎo)亞低溫和維持亞低溫且對神經(jīng)元細(xì)胞的保護(hù)作用優(yōu)于傳統(tǒng)低溫誘導(dǎo)技術(shù)。近來,美國Tang教授領(lǐng)導(dǎo)的團(tuán)隊成功應(yīng)用大麻素受體興奮劑(WIN55等)藥物性誘導(dǎo)亞低溫,并證實該方法能夠改善復(fù)蘇后實驗大鼠的長期生存及神經(jīng)功能預(yù)后[28],實現(xiàn)了低溫方法學(xué)上的又一重大突破。

盡管如此,鑒于多種原因,如臨床醫(yī)師對亞低溫治療缺乏了解、設(shè)備欠缺、缺乏對亞低溫的規(guī)范化管理等,亞低溫治療在國內(nèi)外開展率仍然很低。在深入研究亞低溫治療的同時應(yīng)該開展相關(guān)的學(xué)習(xí),使其能真正應(yīng)用于臨床。

二、藥物保護(hù)

1.血管收縮性藥物:重建重要器官的再灌注在心肺復(fù)蘇術(shù)初期起著很重要的作用,應(yīng)用血管加壓藥增加主動脈舒張壓、冠狀動脈和大腦灌注壓,增加心腦血流灌注,對于腦復(fù)蘇具有最初的意義。腎上腺素用于治療心跳驟?；颊咭延?0余年歷史。該藥物之所以有效,主要是由于α受體作用,尤其是α1受體作用,使全身血管阻力和冠脈灌注壓增加。但與此同時,β1和β2受體作用(包括變力性作用和變時性作用)卻會對CPR造成不利影響。因此,腎上腺素用于心臟驟停的搶救存在爭議，學(xué)者們開始選擇特異性腎上腺素受體激動劑。Tang等[29]通過實驗證明,α2腎上腺素受體激動劑、去甲腎上腺素在復(fù)蘇后能增加大腦灌注壓且無明顯危害。多個研究表明,血管加壓素不但能有效提高冠脈灌注壓和心肌血流量,而且能明顯改善復(fù)蘇后的神經(jīng)功能恢復(fù)[30-31]。

2.自由基清除劑:腦組織缺血再灌注過程中產(chǎn)生的氧自由基具有廣泛的細(xì)胞損傷活性,給予自由基清除劑可以對抗自由基的損傷作用。Kofler等[32]在大鼠CA復(fù)蘇模型中研究了超氧化物歧化酶(superoxide dismutase,SOD)對神經(jīng)功能的保護(hù)作用,發(fā)現(xiàn)SOD過表達(dá)和雌激素聯(lián)合對CA大鼠具有顯著的神經(jīng)保護(hù)作用。研究表明，自由基清除劑依達(dá)拉奉能通過抑制黃嘌呤氧化酶和次黃嘌呤氧化酶的活性,刺激前列環(huán)素的生成,減少炎性介質(zhì)白三烯的產(chǎn)生,降低羥自由基的濃度,從而減輕腦缺血和腦缺血引起的腦水腫及組織損傷,縮小腦梗死面積,還可通過上調(diào)Bcl-2、HSP70蛋白表達(dá)、下調(diào)Bax蛋白表達(dá)減輕大鼠腦缺血再灌注后的細(xì)胞凋亡,增加腦缺血再灌注損傷耐受性,從而起到神經(jīng)保護(hù)作用[33-35]。

3.麻醉或鎮(zhèn)靜藥物:利多卡因最先在貓的腦氣體栓塞模型中被證實有腦保護(hù)作用[36],能夠穩(wěn)定地穿越血腦屏障,通過調(diào)整炎性遞質(zhì),增加神經(jīng)細(xì)胞膜的穩(wěn)定性來保證腦血管的血流供應(yīng)和降低腦代謝[37]。近年研究表明，利多卡因在心肺復(fù)蘇患者中能夠?qū)颊哌M(jìn)行腦保護(hù),有利于患者恢復(fù)自主循環(huán)后的腦恢復(fù)[38]。近年來,學(xué)者們提出了腦保護(hù)的預(yù)處理和后處理概念,其中應(yīng)用最為廣泛的是低濃度吸入型麻醉藥。多項研究表明，2%～4%七氟醚處理60 min以下可通過多種機制起神經(jīng)保護(hù)作用,如抑制調(diào)制蛋白(mincarboxy-terminal modulator protein,CTMP) 活性、減輕海馬CA1 區(qū)膽堿能神經(jīng)元的損傷、抑制小膠質(zhì)細(xì)胞活化、緩解炎性反應(yīng)引起的神經(jīng)元凋亡[39-41]。早在1951年,研究者就發(fā)現(xiàn)巴比妥酸鹽有降低大腦氧消耗量和減少腦血流的作用。但巴比妥類藥物用于腦神經(jīng)保護(hù)仍有爭議[42-43]。

4.其他藥物:人尿中提取的蛋白酶抑制劑—烏司他丁通過抵制腦缺血再灌注損傷而具有保護(hù)作用[44-45];小劑量硫化氫可通過減輕腦水腫,增加海馬區(qū)的巢蛋白而起到腦神經(jīng)保護(hù)作用[46-47];腺苷、雌二醇均有神經(jīng)保護(hù)作用。

三、溶栓保護(hù)

在心搏驟停和心肺復(fù)蘇后出現(xiàn)了凝血功能障礙。在微循環(huán)系統(tǒng)內(nèi)廣泛的血管內(nèi)血栓形成和纖維蛋白沉積導(dǎo)致多器官功能損害。凝血系統(tǒng)和血小板激活不僅加劇了早期大腦灌注失調(diào),而且引起了后期血流灌注不足[48-53]。心肺復(fù)蘇中行溶栓治療的目標(biāo)是對引起心臟驟停的病因進(jìn)行治療,可溶解造成AMI和PE的血栓;對心臟驟停引起的繼發(fā)改變進(jìn)行治療,溶解微血栓,促進(jìn)腦再灌注,減少腦損傷。Fisher等[54]通過對貓的研究發(fā)現(xiàn),n-PA使動物獲得了較完全的腦再灌注并改善了神經(jīng)系統(tǒng)預(yù)后。多項臨床研究表明，心臟驟停后進(jìn)行溶栓治療患者生存率高于非溶栓患者,且有良好的神經(jīng)系統(tǒng)預(yù)后[55-57]。郭曉東等[58]在家兔實驗中證實心臟驟停后在心肺復(fù)蘇時給予溶栓藥物尿激酶可以改善并減輕因細(xì)胞凋亡所致腦神經(jīng)損害。Li等[59]的Meta 分析結(jié)果表明,與非溶栓治療相比,溶栓治療能提高存活率和神經(jīng)系統(tǒng)預(yù)后。對于心臟驟停后溶栓治療的風(fēng)險,多項前瞻性與回顧性研究表明，盡管溶栓本身可增加出血風(fēng)險,但并未能證明溶栓與心肺復(fù)蘇聯(lián)合后會增加出血風(fēng)險[60]。

四、腹部提壓對神經(jīng)系統(tǒng)的保護(hù)

1878年Boehm首次報告胸外按壓術(shù),并于上個世紀(jì)50～60年代間逐步形成心肺復(fù)蘇術(shù),至1960年Kouwenhoven等[61]利用胸外按壓法成功挽救患者的生命,標(biāo)志著現(xiàn)代胸外按壓術(shù)的開始。2000年8月15日AHA在《循環(huán)》雜志上發(fā)表《2000年心肺復(fù)蘇及心血管急救國際指南》,這是首部國際性、科學(xué)性、遵循循證醫(yī)學(xué)的指南。此后于2005、2010、2015年分別對該指南進(jìn)行了改進(jìn)更新。心肺復(fù)蘇在心臟驟停急救中沿用了50多年,但生存出院率卻不理想[62]。神經(jīng)系統(tǒng)損傷更是無法計算。心肺復(fù)蘇按壓和通氣比從最初的15∶2到30∶2,盡管增加了循環(huán),但通氣和循環(huán)被人為分開,通氣時沒有血供,按壓時沒有氧供,這無疑影響各臟器的血氧供應(yīng),大腦作為缺血缺氧的敏感器官受影響更大。為此,王立祥等[63]在Babbs[64]插入式腹部按壓和Geddes等[65]關(guān)于腹部按壓研究基礎(chǔ)上提出了腹部提壓心肺復(fù)蘇術(shù)。腹部提壓較胸外按壓心肺復(fù)蘇、經(jīng)膈肌下抬擠心肺復(fù)蘇、腹部按壓心肺復(fù)蘇能產(chǎn)生更大的潮氣量和分鐘通氣量[66]。王立祥等[67]通過豬模型研究發(fā)現(xiàn)，腹部提壓能產(chǎn)生有效的血流動力學(xué),自主循環(huán)恢復(fù)率與標(biāo)準(zhǔn)心肺復(fù)蘇無統(tǒng)計學(xué)意義,這表明腹部提壓可產(chǎn)生有效的心肺復(fù)蘇,可用于心臟驟停的搶救。同時,臨床研究也發(fā)現(xiàn),在胸部創(chuàng)傷等存在傳統(tǒng)心肺復(fù)蘇禁忌癥患者中,腹部提壓能提高復(fù)蘇成功率,為腦復(fù)蘇奠定了基礎(chǔ)[68]。多個臨床觀察研究指出與傳統(tǒng)CPR相比,采用腹部提壓心肺復(fù)蘇患者,心率、平均動脈壓、氧分壓和二氧化碳分壓明顯優(yōu)于傳統(tǒng)心肺復(fù)蘇[69-72]?？偟膩碚f,腹部提壓可提供有效心肺復(fù)蘇和更大潮氣量及通氣量,于是我們判斷:相對于標(biāo)準(zhǔn)CPR,腹部提壓對神經(jīng)元細(xì)胞損傷有保護(hù)作用,為此,下一步將通過豬模型對其進(jìn)行深入研究。

五、總結(jié)

從最初的心肺復(fù)蘇到現(xiàn)在的心肺腦復(fù)蘇，體現(xiàn)了研究者對腦復(fù)蘇的重視程度在不斷加大。隨著對腦復(fù)蘇研究的不斷深入,腦復(fù)蘇的治療手段也不斷增多,但療效仍不能令人滿意。有文獻(xiàn)報道,患者在院外進(jìn)行心肺復(fù)蘇并成功存活且無明顯腦功能損害的患者僅有5%[73]。這表明腦復(fù)蘇對各臨床研究者來說仍任重而道遠(yuǎn),我們急需尋找更有效的腦復(fù)蘇治療手段。

1 葛均波,徐永健.內(nèi)科學(xué)[M].8版.北京:人民衛(wèi)生出版社,2013:329.

2 Mozaffarian D,Benjamin EJ,Go AS,et al.Heart disease and stroke statistics—2015 update:a report from the American Heart Association[J].Circulation,2015,131(4):e29-e322.

3 馬青變,鄭亞安.2016年國際復(fù)蘇聯(lián)絡(luò)委員會/美國心臟協(xié)會心臟驟停后體溫管理建議解讀[J].中國醫(yī)刊,2016,51(10):17-20.

4 Nichol G,Thomas E,Callaway CW,et al.Regionaol variation in out-of-hospital cardiac arrest incidence and outcome[J].JAMA,2008,300(12):1423-1431.

5 Chan PS,McNally B,Tang F,et al.Recent trends in survival from out-of-hospital cardiac arrest in the United States[J].Circulation,2014,130(21):1876-1882.

6 Goldberger ZD,Chan PS,Berg RA,et al.Duration of resuscitation effortsand survival after in-hospital cardiac arrest:an observational study[J].Lancet,2012,380(9852):1473-1481.

7 Janata A,Holzer M.Hypothermia After Cardiac Arrest[J].Crit Care Med,1991,19(3):168-179.

8 Engel H,Ben Hamouda N,Portmann K,et al.Serum procalcitonin as a marker of post-cardiac arrest syndrome and long-term neurological recovery,but not of early-onset infections,in comatose post-anoxic patients treated with therapeutic hypothermia[J].Resuscitation,2013,84(6):776-781.

9 Bigel WG,Lindsay WK,Greenwood WF.Hypothermia its possible role in cardiac surgery:an investigation of factors governing survial in dogs at low body temperatures[J].Ann Surg,1950,132(5):849-866.

10 Busto R,Dietrich WD,Globus MY,et al.Small Differences in Intraischemic Brain Temperature Critically Determine the Extent of Ischemic Neuronal Injury[J].J Cereb Blood Flow Metab,1987,7(6):729-738.

11 Jiang J,Yu M,Zhu C.Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury:1-year follow-up review of 87 cases[J].J Neurosurg,2000,93(4):546-549.

12 江基堯,朱誠.國外亞低溫與腦損傷的研究進(jìn)展[J].國外醫(yī)學(xué)神經(jīng)病學(xué)神經(jīng)外科學(xué)分冊,1993,20(1):4-7.

13 Tsai MS,Barbut D,Tang W,et al.Rapid head cooling initiated coincident with cardiopulmonary resuscitation improves success of defibrillation and postresuscitation myocardial function in a porcine model of prolonged cardiac arrest[J].J Am Coll Cardiol,2008,51(20):1988-1990.

14 Hypothermia After Cardiac Arrest Study Group.Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest[J].N Engl J Med,2002,346(8):549-556.

15 Bernard SA,Gray TW,Buist MD,et al.Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia[J].N Engl J Med,2002,346(8):557-635.

16 Abella BS,Zhao D,Alvarado J,et al.Intra-arrest cooling improves outcomes in a murine cardiac arrest model[J].Circulation,2004,109(22):2786-2791.

17 Peberdy MA,Callaway CW,Neumar RW,et al.Part 9:post-cardiac arrest care:2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care[J].Circulation,2010,122(18 Suppl 3):768-786.

18 Deakin CD,Nolan JP,Soar J,et al.European Resuscitation Council guidelines for resuscitation 2010 section 4:adult advanced life support[J].Resuscitation,2010,81(10):1305-1352.

19 花嶸,李春盛.亞低溫用于心搏驟停后腦保護(hù)的研究進(jìn)展[J].中華急診醫(yī)學(xué)雜志,2010,19(10):1109-1111.

20 Lampe JW,Becker LB.State of the art in therapeutic hypothermia[J].Annu Rev Med,2011,62(1):79-93.

21 Tortorici MA,Kochanek PM,Poloyac SM.Effects of hypothermia on drug disposition,metabolism,and response:A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system[J].Crit Care Med,2007,35(9):2196-2204.

22 Polderman KH,Herold I.Therapeutic hypothermia and controlled normothermia in the intensive care unit:practical considerations,side effects,and cooling methods[J].Crit Care Med,2009,37(3):1101-1120.

23 Ye S,Weng Y,Sun S,et al.Comparison of the durations of mild therapeutic hypothermia on outcome after cardiopulmonary resuscitation in the rat[J].Circulation,2012,125(1):123-129.

24 Abella BS,Zhao D,Alvarado J,et al.Intra-arrest cooling improves outcomes in a murine cardiac arrest model[J].Circulation,2004,109(22):2786-2791.

25 Kim F,Olsutka M,Longstreth WT Jr,et al.Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients witll a rapid infusion of 4 degrees C normal saline[J].Circultion,2007,115(24):3064-3070．

26 廖曉星,胡春林,文潔,等.兔心肺復(fù)蘇后經(jīng)腹腔誘導(dǎo)亞低溫的研究[J].中華急診醫(yī)學(xué)雜志,2010,19(1):16-20.

27 魏紅艷,廖曉星,李欣,等.腹腔降溫對心肺復(fù)蘇后兔海馬神經(jīng)損傷的影響[J].中華急診醫(yī)學(xué)雜志,2012,21(10):1116-1121.

28 Sun S,Tang W,Song F,et al.Pharmacologically induced hypothermia with cannabinoid receptor agonist WIN55,212-2 after cardiopulmonary resuscitation[J].Crit Care Med,2010,38(12):2282-2286.

29 Huang L,Tang W.Vasopressor agents:old and new components[J].Curr Opin Crit Care,2004,10 (3):183-187.

30 Wenzel V,Lindner KH,Krismer AC,et al.Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs[J].J Am Coll Cardiol,2000,35(2):527-533.

31 Ristagno G,Sun S,Tang W,et al.Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation[J].Crit Care Med,2007,35(9):2145-2149.

32 Kofler J,Hurn PD,Traystman RJ.SOD1 overexpression and female sex exhibit region-specific neuroprotection after global cerebral ischemia due to cardiac arrest[J].J Cereb Blood Flow Metab,2005,25(9):1130-1137.

33 Yoshida H,Yanai H,Namiki Y,et al.Neuroprotective effects of edaravone:a novel free radical scavenger in cerebrovascular injury[J].CNS Drug Rev,2006,12(1):9-20.

34 黃承紅,蔡志友,曾令瓊,等.依達(dá)拉奉對腦出血患者血清IL-1β、TNF-α影響的研究[J].重慶醫(yī)學(xué),2008,37(7):728-729.

35 鄺桐博,皋聰,季暉.自由基清除劑依達(dá)拉奉的藥理作用研究進(jìn)展[J].安徽醫(yī)藥,2014,18(5):804-807.

36 Evans DE,Kobrine AI,LeGrys DC,et al.Protective effect of lidocaine in acute cerebral ischemia induced by air embolism[J].J Neurosurg,1984,60(2):257-263.

37 Mitchell SJ.Lidocaine in the treatment of decompression illness:areview of the literature[J].Undersea Hyperb Med,2001,28(3):165-174.

38 趙慧.利多卡因在心肺復(fù)蘇中腦保護(hù)作用的研究[J].黑龍江醫(yī)藥,2016,29(4):648-646.

39 Chen Y,Nie H,Tian L,et al.Sevoflurane preconditioning-induced neuroprotection is associated with Akt activation via carboxy-terminal modulator protein inhibition[J].Br J Anaesth,2015,114(2):327-335．

40 Hu X,Zhang Y,Li W,et al．Preconditioning with sevoflurane ameliorates spatial learning and memory deficit after focal cerebral ischemia-reperfusion in rats[J].Int J Dev Neurosci,2013,31(5):328-333．

41 Li XQ,Cao XZ,Wang J,et al.Sevoflurane preconditioning ameliorates neuronal deficits by inhibiting microglial MMP-9 expression after spinal cord ischemia/reperfusion in rats[J].Mol Brain,2014,7(1):1-14.

42 Reid KH,Paskitti M,Guo SZ,et al.Experience with ketamine and sodium pentobarbital as anesthetics in a rat model of cardiac arrest and resuscitation[J].Resuscitation,2003,57(2):201-210.

43 Behringer W,Kentner R,Wu X,et al.Thiopental and phenytoin by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 minutes in dogs.An exploratory study[J].Resuscitation,2001,49(1):83-97.

44 Koga Y,Fujita M,Tsuruta R,et al.Urinary trypsin inhibitor suppresses excessive superoxide anion radical generation in blood,oxidative stress,early inflammation,and endothelial injury in forebrain ischemia/reperfusion rats[J].Neurol Res,2010,32(9):925-932．

45 Yano T,Anraku S,Nakayama R,et al.Neuroproteetive effect of urinary trypsin inhibitor against focal cerebral ischemia—reperfusion injury in rats[J].Anesthesiology,2003,98(2):465-473．

46 Ren C,Du A,Li D,et al.Dynamic change of hydrogen sulfide during global cerebral isehemia—reperfusion and its effect in rats[J].Brain Research,2010,1345(2):197-205．

47 郭濤,黃亮,曹春水,等.硫化氫對大鼠心肺復(fù)蘇后腦水腫及海馬區(qū)Nestin表達(dá)的影響[J].中華急診醫(yī)學(xué)雜志,2012,21(1):18-23.

48 Wetsch WA,Sp?hr F,Teschendorf P,et al.Thrombolysis during cardiopulmonary resuscitation[J].Dtsch Med Wochenschr,2010,135(40):1983-1988．

49 Adrie C,Laurent I,Monchi M,et al.Postresuscitation disease after cardiac arrest:a sepsis-like syndrome[J].Curr Opin Crit Care,2004,10(3):208-212．

50 Janata K,Holzer M,Kurkciyan I,et al.Major bleeding complications in Cardiac arrest due to massive pulmonary embolism[J].Resuscitation,2003,57(1):49-55．

51 Laver S,Farrow C,Turner D,et al.Mode of death after admission to an intensive care unit following cardiac arrest[J].Intensive Care Med,2004,30 (11):2126-2128．

52 Snyder-Ramos SA,B ttiger BW.Molecular markers of brain damage——clinical and ethical implications with particular focus on cardiac arrest[J].Restor Neurol Neurosci,2003,21(3-4):123-139．

53 Adrie C,Laurent I,Monchi M,et a1.Postresusoitatiou disease after cardiac arrest:a sepsis-like syndrome[J].Curr Opin Crit Care,2004,10(3):208-212．

54 Fisher M,Hossmann KA.No-reflow after cardiac arrest[J].Intensive Care Med,1995,21(2):132-141．

55 Ruiz-Bailén M,Aguayo-de-Hoyos E,Serrano-Córcoles MC,et al.Thrombolysis with recombinant tissue plasminogen activator during cardiopulmonary resuscitation in fulminant pulmonary embolism.A case series[J].Resuscitation,2001,51(1):97-101.

56 Voipio V,Kuisma M,Alasp?? A,et al.Thrombolytic treatment of acute myocardial infarction after out-of-hospital cardiac arrest[J].Resuscitation,2001,49(49):251-258.

57 Schreiber W,Gabriel D,Sterz F,et al.Thrombolytic therapy after cardiac arrest and its effect on neurological outcome[J].Resuscitation,2002,52(1):63-69.

58 郭曉東,張巍,郭靜,等.尿激酶對家兔心肺復(fù)蘇后腦神經(jīng)細(xì)胞凋亡的影響[J]．武警醫(yī)學(xué),2015,26(12):1216-1220.

59 Li X,Fu QL,Jing XL,et al.A meta-analysis of cardiopulmonary resuscitation with and without the administration of thrombolytic agents[J].Resuscitation,2006,70(1):31-36.

60 Sp?hr F,B?ttiger BW.Safety of thrombolysis during cardiopulmonary resuscitation[J].Drug Saf,2003,26(6):367-379.

61 Kouwenhoven WB,Jude JR,Knickerbocker GG．Closed-chest cardiac massage[J]．JAMA,1960,173:1064-1067．

62 Field JM,Hazinski MF,Sayre MR,et al.Part 1:executive summary:2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care[J].Circulation,2010,122 (18 Suppl 3):S639-S656.

63 王立祥,鄭靜晨.單純腹部提壓:一種心肺復(fù)蘇的新方法[J].中國危重病急救醫(yī)學(xué),2009,21(6):323-324.

64 Babbs CF.Interposed abdominal compression CPR:a comprehensive evidence based review[J].Resuscitation,2003,59(1):71-82．

65 Geddes LA,Rundell A,Lottes A,et a1.A new cardiopulmonary resuscitation method using only rhythmic abdominal compression:a preliminary report[J].Am J Emerg Med,2007,25(7):786-790．

66 馬立芝,王立祥,李秀滿,等.腹部按壓心肺復(fù)蘇方法對呼吸驟停豬肺通氣的觀察[J].中華臨床醫(yī)師雜志,2011,5(12):3623-3624.

67 劉亞華,王立祥.腹部提壓法對心搏驟停豬血流動力學(xué)影響的實驗研究[C].中國危重病醫(yī)學(xué)大會-2011暨北京醫(yī)學(xué)會重癥醫(yī)學(xué)年會匯編,北京,2011.631-632[2017-03-25].

68 張思森,孟志劍,劉青,等.腹部提壓心肺復(fù)蘇術(shù)在胸部創(chuàng)傷患者院前急救中的應(yīng)用[J/CD].中華衛(wèi)生應(yīng)急電子雜志,2015,1(1):32-34.

69 Zhang S,Liu Q,Han S,et al．Standard versus Abdominal Lifting and Compression CPR[J].Evid Based Complement Alternat Med,2016,2016(1-2):1-8.

70 劉青,張思森,彭丹洋,等.腹部提壓法急救復(fù)蘇效果臨床觀察[J].中華危重病急救醫(yī),2015,27(12):1011-1012.

71 戚文濤,彭丹洋,張思森,等.腹部提壓心肺復(fù)蘇法救治心搏驟停臨床療效觀察:附57 例病例報告[J].中華危重病急救醫(yī)學(xué),2016,28(7):654-656.

72 王國濤,張思森,劉青,等.腹部提壓心肺復(fù)蘇臨床應(yīng)用研究:附40例報告[J].中華急診醫(yī)學(xué)雜志,2015,24(11),1264-1267.

73 Newman DH,Greenwald I,Callaway CW.Cardiac arrest and the role of thrombolytic agents[J].Ann Emerg Med,2000,35(5):472.

10.3877/cma.j.issn.2095-9133.2017.04.010

河南省醫(yī)學(xué)科技攻關(guān)計劃項目(201303221);河南省鄭州科技攻關(guān)計劃項目(131PPTGG380-2);河南省鄭州科技領(lǐng)軍人才重點項目(131PLJRC682);實用新型專利(ZL 200920164343.6,ZL 200920160376.3,ZL 2014 3 0044027.1)

450003 鄭州,南方醫(yī)科大學(xué)附屬鄭州人民醫(yī)院急診科

張思森,Email:2362176700@qq.com

2017-03-25)

(本文編輯:李建忠)

岑穎欣,張思森.腦復(fù)蘇臨床研究進(jìn)展[J/CD].中華衛(wèi)生應(yīng)急電子雜志,2017,3(4):238-241.