海军军医大学学报  2023, Vol. 44 Issue (9): 1026-1029   PDF    
急性缺血性脑卒中机械取栓术后血压管理研究进展
张小曦, 杨鹏飞, 张永巍, 刘建民     
海军军医大学(第二军医大学)第一附属医院脑血管病中心, 上海 200433
摘要: 机械取栓是大血管闭塞急性缺血性脑卒中(AIS)患者的有效治疗方法,但是超过半数的患者临床预后不佳。术后高灌注导致的颅内出血转化与AIS机械取栓术后临床预后恶化密切相关,而低灌注可能会导致梗死进一步加重,因此,加强术后血压管理、平衡好颅内高灌注与低灌注风险对于改善患者预后具有重要意义。ENCHANTED2/MT研究旨在探讨机械取栓后强化降压治疗的效果,一经开展即在国内外脑血管病领域引起广泛关注。本文综合目前脑血管病领域最重要的研究结果,对AIS机械取栓后血压管理的研究进展进行解读。
关键词: 急性缺血性脑卒中    血压管理    机械取栓    个体化治疗    
Post-thrombectomy blood pressure management of acute ischemic stroke: research progress
ZHANG Xiaoxi, YANG Pengfei, ZHANG Yongwei, LIU Jianmin     
Neurovascular Center, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China
Abstract: Mechanical thrombectomy is an effective treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion, but more than half of the patients have poor clinical prognosis. The transformation of intracranial hemorrhage caused by postoperative high perfusion is closely related to the deterioration of clinical prognosis after AIS mechanical thrombectomy, and low perfusion may lead to further aggravation of infarction. Therefore, strengthening postoperative blood pressure management and balancing the risks of intracranial high perfusion and low perfusion are of great significance for improving patient prognosis. ENCHANTED2/MT research is to explore the effect of intensive antihypertensive therapy after mechanical thrombectomy, and it immediately attracts widespread attention in the field of cerebrovascular diseases at home and abroad. This article summarizes the most important research in the field of cerebrovascular diseases, and interprets the research progress in blood pressure management after AIS mechanical thrombectomy.
Key words: acute ischemic stroke    blood pressure management    mechanical thrombectomy    individualized therapy    

脑卒中是全球范围内引起成年人群死亡与残疾的首要病因[1]。2015年,全球新发卒中患者人数为900万,既往卒中幸存者人数4 200万,伤残调整生命年(disability-adjusted life year,DALY)超过1亿[2]。据统计,我国卒中发病率和死亡率分别为247/10万人年和115/10万人年,估测每年新发卒中人数达240万,卒中相关死亡人数110万,既往有卒中发作史的幸存人数达1 110万[3]。全球的卒中疾病负担严重,然而急性缺血性脑卒中(acute ischemic stroke,AIS)急性期治疗措施的临床证据进展缓慢。

对于AIS患者,尽早恢复血流灌注是减少远期神经功能缺损的最有效措施。AIS目前最主要的治疗方式包括静脉溶栓(阿替普酶或重组人纤溶酶原复合物)与机械取栓(支架取栓或抽吸装置),机械取栓是大血管闭塞AIS首选治疗策略。由于颅内高灌注与低灌注均存在风险,血管再通后的血压管理成为影响AIS患者预后的关键因素,但目前血管再通后血压的最佳控制范围尚未达成共识。2019年ENCHANTED研究探讨了强化降压对于接受溶栓治疗的高收缩压AIS患者预防再出血的效果,结果显示将24 h内收缩压控制在<140 mmHg(1 mmHg=0.133 kPa)甚至低至110~120 mmHg能够改善患者神经功能[4],并且可能不会因为降低灌注而增加脑梗死面积[5]。为进一步探讨机械取栓后强化降压治疗的效果,海军军医大学(第二军医大学)第一附属医院脑血管病中心刘建民教授与乔治全球健康研究院Anderson教授共同发起开展了ENCHANTED2/MT研究[6],在国内外脑血管病领域引起广泛关注。本文对AIS机械取栓后血压管理的研究进展进行综述,以期为合理选择降压治疗策略提供参考。

1 体循环血压影响颅内灌注压,与临床预后密切相关

虽然机械取栓显著提高了大血管闭塞型AIS患者的成功再通率,但是超过半数的患者临床预后不佳[7]。从病理生理学机制而言,梗死区域脑组织血流调节能力下降,因此体循环血压对颅内压的影响被放大,体循环血压过高可能导致颅内灌注压突破进而导致出血转化,而体循环压力过低可能导致外周重要脏器灌注压不足,以及梗死区域侧支代偿能力下降,进而导致梗死进一步加重[8-9]。因此,平衡好颅内高灌注和低灌注风险是体循环血压管理的重要衡量标准。

然而,目前多数指南对于机械取栓围手术期血压管理的目标设定较为宽泛,多为不高于180/105 mmHg,推荐级别参差不齐[10]。例如,2018年,美国心脏协会(American Heart Association,AHA)/美国卒中协会(American Stroke Association,ASA)指南推荐再灌注治疗期间维持血压≤180/105 mmHg,血管再通后的24 h内维持血压<180/105 mmHg[11]。然而,上述推荐主要是依据静脉重组人纤溶酶原复合物溶栓的相关证据,而关于机械取栓术后的血压管理证据尚欠缺。Maier等[12]研究结果显示血管内治疗后收缩压均值>141 mmHg和收缩压最大值>159 mmHg可预测不良结果。另外,AIS患者往往病情复杂,血压受基础病史、侧支代偿、梗死体积、交感反射等诸多因素的影响,不同地区的血压管理方案也存在差异[13]。因此,实现标准化、规范化的血压管理是进一步改善患者临床预后的重要手段。

2 机械取栓围手术期最佳血压目标值尚无定论

目前仍缺乏机械取栓术后降压治疗效果及最佳的血压管理目标值的强力证据。一项纳入了7项随机对照试验(MR CLEAN、ESCAPE、EXTEND-IA、SWIFT PRIME、REVASCAT、PISTE、THRACE)的meta分析提示,对于基线收缩压≥140 mmHg的患者,收缩压与临床预后恶化相关(调整后合并OR为0.86,95% CI 0.81~0.91),而对于基线收缩压<140 mmHg的患者两者无明显相关性[14]。在临床实践中,有学者认为血管再通前维持较高的血压可以改善侧支代偿和缺血脑组织的灌注,接受血管内治疗的患者术中应维持140~180 mmHg的收缩压,术后根据血管再通状态调整血压管理策略[15]。也有一些学者认为应将收缩压降至正常水平(120~140 mmHg)以降低出血转化风险[16]。美国一项研究对58家医疗机构进行调研,结果显示大多数机构认为未成功再通的患者收缩压应维持≤180 mmHg,而对于成功再通的患者,21家(36%)机构的收缩压目标为120~139 mmHg,12家(21%)为140~159 mmHg,16家(28%)为≤180 mmHg[17]。对于机械取栓的AIS患者,也有研究提示入院时血压值较高与侧支循环代偿差、再通效果差及不良事件的增加相关[18]

Mulder等[19]对MR CLEAN研究进行事后分析,结果显示基线收缩压与神经功能预后之间呈“U”形相关,即血压偏高或偏低均与不良预后相关,且最佳收缩压为120 mmHg。一项前瞻性队列研究纳入217例机械取栓后成功再通的大血管闭塞AIS患者,按照术后血压将其分为3组:强化降压组(<140/90 mmHg)、中度降压组(<160/90 mmHg)及允许性高血压组(<220/110 mmHg,接受静脉溶栓预处理的患者为<180/105 mmHg)。该研究结果显示,较高的收缩压最大值与3个月死亡率增加和不良功能预后相关[20]。Martins等[21]通过一项纳入674例接受急性期再灌注治疗(静脉溶栓或动脉内治疗)的AIS患者的回顾性队列研究显示,对于未成功血管再通的患者,24 h内血压与功能预后呈“J”型相关,而对于成功血管再通的患者,则呈现连续的线性相关。除此之外,Goyal等[22]发现机械取栓后首个24 h内血压波动程度与不良预后相关。

2018年AHA指出,再通前维持允许性高血压(180/110 mmHg)可改善侧支代偿[11]。但一项随机对照试验预备研究结果显示全麻状态下的机械取栓术中升高血压(160~180 mmHg vs 130~150 mmHg)不能改善患者临床预后[23],多数临床研究将术中血压目标维持在140~180 mmHg[24-25]

3 机械取栓术后血压管理的随机对照试验

BP-TARGET研究是首个探讨机械取栓后血压管理的随机对照试验,该研究纳入324例受试者,比较了收缩压100~129 mmHg和130~185 mmHg对术后24~36 h出血转化风险的影响,结果显示100~129 mmHg并未显著降低出血转化风险(调整后OR为0.96,95% CI 0.60~1.51,P=0.84),两组间临床预后差异没有统计学意义[26]。ENCHANTED2/MT研究是目前样本量最大的随机对照试验,该研究旨在探讨对于机械取栓后获得血管成功再通的大血管闭塞AIS患者,强化降压治疗(收缩压<120 mmHg)在改善患者功能预后(90 d改良Rankin量表评分序贯分析)方面是否优于较高水平(收缩压140~180 mmHg)的血压管理策略。ENCHANTED2/MT研究拟纳入2 257例受试者,中期分析时由于提前达到安全终点而提前终止,最终纳入821例受试者,该研究首次证实收缩压<120 mmHg的降压策略有害(合并OR为1.37,95% CI 1.07~1.76),探明了安全管理的下限[6]。OPTIMAL-BP研究旨在评估强化降压与传统血压控制对动脉内治疗后成功血管再通的患者的效果[27],并在2023年欧洲卒中大会上发布了结果。该研究共纳入306例受试者,强化降压组(收缩压<140 mmHg)术后3个月良好预后(改良Rankin量表评分0~2分)率差于对照组(收缩压140~180 mmHg)(39.4% vs 54.4%;调整后OR为0.56,95% CI 0.33~0.96),这与ENCHANTED2/MT研究结果类似。OPTIMAL-BP研究由于安全性考虑提前终止。事实上,大部分学者仍然坚持强化降压是正确的,但降压时机和降压策略仍需进一步研究。

此外,同时期正在开展的临床随机对照试验还包括CRISIS-Ⅰ、BEST-Ⅱ、PRESS、DETECT、INDIVIDUATE等10余项研究。这些研究纳入人群存在异质性,因此具有不同的外部有效性,例如,INDIVIDUATE和PRESS将个体化血压作为强化降压目标值,ENCHANTED2/MT和OPTIMAL-BP不仅纳入前循环大血管闭塞AIS患者,同时保留了后循环大血管闭塞AIS患者。上述研究的亚组研究可以为血压管理提供更多高级别循证医学证据,并为不同人群的血压管理提供证据。

4 小结

目前,针对大血管闭塞AIS患者机械取栓血管再通后的血压管理策略已取得如下共识:(1)血管再通后强化降压管理不能显著降低症状性出血转化风险和死亡风险,而可能增加临床预后不良风险;(2)血管再通后合理的血压管理可改善临床预后,但即刻启动强化降压可能是有害的,启动强化降压治疗的时机仍待进一步研究;(3)血管再通后收缩压控制的安全下限为120 mmHg,但也可能更高。血管再通后的最佳血压目标值、降压药物的选择、降压速度等诸多问题仍待进一步研究。

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