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    急性腦梗死溶栓治療的新進展

    來源:萬方期刊網  時間:2018-04-16 11:25:29  點擊:

      【摘要】急性腦梗死的發病率、病死率與致殘率極高,臨床治療以溶栓與降纖及循環改善、抗血小板聚集、神經保護治療為主,其中,溶栓治療是最為有效、最為直接的治療方法。本文將從急性腦梗死溶栓治療的依據與藥物選擇、時間窗、治療方式及并發癥等方面進行綜述報道。

      【關鍵詞】急性腦梗死;溶栓治療;研究進展

      急性腦梗死是老年多發病,隨著我國逐步步入到老齡化社會,該病發病率也在逐年攀升,嚴重威脅到老年人生命健康安全。急性腦梗死是指局部供血堵塞或者中斷造成的腦組織缺血缺氧、壞死的過程,伴有不同程度的神經功能損傷與特征變化,是僅次于惡性腫瘤的第二大致死與致殘原因。急性腦梗死臨床治療方法較多,溶栓與循環改善、抗血小板聚集、神經保護是常見方法,溶栓治療應用最廣,認同率最高,且隨著溶栓時間認識與溶栓技術進步下,溶栓治療急性腦梗死的價值日漸凸顯,現就相關研究進展綜述如下。

      1 溶栓治療的依據

      經臨床證實,急性缺血性腦梗死病變中心區腦組織已經出現了損害,這種損害是不可逆的,組成缺血性急性腦梗死區域的缺血半暗帶區的側支循環依然存在,依然可以獲得血液供給,且神經細胞功能未完全消失可以在短時間內存活,這種狀態依然是可逆的,腦代謝障礙恢復的前提是有效時間內及時將血液供應恢復,才能使神經細胞功能相應恢復。病理學研究還顯示,當缺血中心區的腦血流閥值為10ml/100g/min時將出現神經細胞膜離子泵與細胞能量代謝的衰竭,此時出現的損害是不可逆的[1]。缺血半暗帶的腦血流在電衰竭與能量衰竭之間時,側支循環與大動脈殘留血流依然在局部腦組織中存在,且有部分神經元存活[2]。由此,將缺血半暗帶恢復是溶栓治療的關鍵步驟,也是治療急性腦梗死的有效途徑。

      2 確定溶栓治療時間窗

      即使腦梗死半暗帶區域內的神經細胞通過側支循環可以確保血液供應維持一段時間,但是并不能長期維持,維持時間大致5.5~7h,將此階段作為溶栓治療的最佳時機。但是大部分患者在發病6h進行溶栓治療,僅有少數患者在該溶栓時間窗內接受治療。NiNDS試驗充分顯示,溶栓在發病3h內實施,溶栓治療2個月后神經功能恢復效果優于使用安慰劑的患者,且病死率得到控制。ECASSIII也顯示了3h內應用重組型纖溶酶原激活劑的患者預后效果最佳。Lees的報道也顯示了急性腦梗死患者發病4~5h內使用重組型纖溶酶原激活劑療效更為顯著,治療時間越早,效果越顯著[3]。反之,如果發病4.5h后使用重組型纖溶酶原激活劑治療則風險較大。大部分研究均顯示了發病3h、6h及3~4.5h是最佳溶栓時間窗。也有研究顯示[4],不同時間窗3h時間窗動脈或者靜脈溶栓的效果最佳,低于3h時間窗靜脈溶栓與動脈溶栓療效存在一致性,但總體看來,所用時間最短的是靜脈溶栓干預,且創傷小、效果更為顯著。

      3 選擇好溶栓治療藥物

      急性腦梗死超早期治療的首選方法為溶栓治療已經得到循證醫學的證實,當前應用較多的溶栓藥物為尿激酶(uk)與rt-pA,rt-pA是第2代溶栓藥物,纖維蛋白特異性顯著,是一種選擇性較高的纖維酶原激活劑,作用是促纖維蛋白溶酶原轉變為纖維蛋白溶酶,但是產生全身抗凝與纖溶狀態的情況并不多見,已經被當成治療腦梗死的一線類藥物[5]。但是該藥物有一定缺點,有著較短的半衰期,為3.5min,且進入到血栓時的穿透力較低,但是可以與纖維蛋白表面結合,將血流再通延遲,將血管再阻塞的風險降低。uK則是第一代溶栓藥物,半衰期更長,為15min左右,是一種更為直接的纖溶酶原激活劑,溶栓效果也更為顯著。但依然存在一些不足,比如,有著較差的選擇性,可以對血液中的纖維蛋白原與血栓中的纖維蛋白同時溶解,非常容易出現出血風險。由此可見,兩種溶栓藥物各有優勢與不足,在推廣使用的廣泛性上uK要優于rt-pA。

      4 溶栓治療方法

      當前,溶栓治療方法主要以靜脈與動脈溶栓治療為主。①靜脈溶栓。靜脈溶栓的速度更快,操作簡單、給藥更加及時、創傷更小、費用更為低廉,可以在急性期應用還可以很好的控制在溶栓時間窗內,這是靜脈溶栓的優勢;而缺點是頸內動脈與大腦中動脈(MCA)主干閉塞再通率較低,且靜脈全身給藥,有著大劑量用藥要求,也促使并發癥與不良反應發生率增大。uK100~160萬U溶解于0.9%的氯化鈉注射液100~200ml靜脈滴注,滴注前15min先滴入量為總滴入量的2/3,后20min滴入量為滴入總量的1/3。rt-pA0.9mg/kg,1min內靜脈推注10%,剩余以持續靜脈滴注1h的方式給藥。有報道顯示[6],早期溶栓治療應用rt-pA可以將病死率與致殘率降低,療效顯著。②動脈溶栓。選擇性高、副作用與不良反應少、用藥劑量小、局部用藥濃度高、血管再通性高是主要優勢;不足是操作要求高,需進行DSA檢查,費用較高,很難在基層醫院推廣應用,且容易使整個腦血流處于高凝狀態,危險性大。臨床以頸動脈溶栓治療為主,使用尿激酶60~100萬U,將其溶解于20ml的生理鹽水中可作為行動脈加壓注射的藥物。有研究顯示,給藥后,梗死病灶局部藥物濃度要較同等靜脈給藥高,動脈溶栓效果更為顯著,且出血及不良反應更少。一項隨機對照試驗結果顯示,急性腦梗死患者使用uK溶栓治療,6h內動脈注射給藥,實驗組72的Rankin評分與血管再通率均較安慰劑組高[7]。大部分急性腦梗死患者有溶栓治療禁忌癥,容易錯失溶栓時間窗的患者可以選擇血管介入溶栓治療,可以將局部藥物濃度增加,將溶栓速度提高,將治療時間縮短,進而增強溶栓治療成功率。

      5 溶栓治療并發癥

      溶栓治療后阻塞血管可得到再通,將灌注恢復,進而將梗死面積縮小,有效控制病情,但是無論是靜脈溶栓還是動脈溶栓均會不可避免的出現并發癥,常見并發癥有出血、再灌注損傷與腦血管再閉塞。其中,出血以靜脈溶栓時的微血尿為主,但治療后自動消失,動脈溶栓腦內出血多見,再灌注損傷常見3h后溶栓的患者,可能與脂質含量及自由基過多、鈣離子快速內流等有關[8]。腦血管再閉塞是指應用溶栓藥物后殘留的血栓容易使再閉塞發生率提高。

      綜上所述,急性腦梗死早期溶栓治療是最為有效、快速的方法,對中度、重度神經障礙患者有一定療效,在應用上需掌握好時間窗、控制并防范并發癥,掌握各種適應證與用藥方法,才能使治療安全、有效進行。

      【參考文獻】

      [1]徐玲玲. 動脈溶栓治療急性腦梗死的研究進展[J]. 中國實用神經疾病雜志,2014,17(02):103-105.

      [2]蔣柳結,歐念飛,李紹東,等.急性腦梗死動脈內溶栓治療療效及安全性[J].中國實用神經疾病雜志, 2010,13(21): 38-40

      [3]李鋼,蔡曉斌. 動-靜脈聯合溶栓治療急性腦梗死的臨床進展[J]. 醫學理論與實踐,2014,27(20):2695-2696.

      [4]呂俊彬.急性腦梗死溶栓治療的時間窗選擇與療效分析[J].陜西醫學雜志,2013,42(08):969-970

      [5]何世發,華杰.靜脈溶栓治療急性腦梗死32例療效分析[J].中國社區醫師(醫學專業),2012,14(18):184-185

      [6]陳淑芬,韓翔,史朗峰,等.急性期腦梗死靜脈溶栓治療的有效性評價[J].中華腦血管病雜志(電子版),2009,03(06):275-282

      [7]王江敏. 急性腦梗死的溶栓療法及研究進展[J]. 中國醫藥指南,2013,11(03):578-579.

      [8]付佳.靜脈溶栓與動脈溶栓治療急性腦梗死的療效對比[D].長春:吉林大學,2013

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