肺动脉高压的危险分层评估及管理

2021-06-04 《门诊》杂志 门诊新视野

既往研究认为,采用B型钠尿肽(BNP)或N端-B型钠尿肽前体(NT-proBNP)及六分钟步行距离即可完美地对肺动脉高压(PAH)患者的病情轻重进行有效分析。

既往研究认为,采用B型钠尿肽(BNP)或N端-B型钠尿肽前体(NT-proBNP)及六分钟步行距离即可完美地对肺动脉高压(PAH)患者的病情轻重进行有效分析。然而,越来越多的临床研究表明,单一预测因素远远不能满足临床需要,而通过整合多种因素,对具有潜在风险的患者进行危险分层评估,并基于该危险评估结果采取针对性的治疗策略,可给PAH患者带来更大获益,因此受到业内医师关注。

PAH风险预测工具

目前,国际上主要有6种PAH风险预测工具,包括NIH registry equation(可预测生存率)、French network equation、PH Connection (PHC) equation、Scottish composite score、REVEAL equation and risk score(较为常用)、ESC/ERS risk stratificaiton table(较为常用)。

为了让国内医师更加便利地进行PAH风险分层,2018年《中国肺高血压诊断和治疗指南》(以下简称“指南”)提出了我国的PAH危险分层方法。该分层方法使用简便,只需获得患者心功能分级、6分钟步行距离、NT-proBNP水平、右心房压、心指数及混合静脉血氧饱和度,即可将患者分为低危、中危及高危人群。(表1)

表1. 我国成人肺动脉高压患者危险分层

不同危险分层对应的治疗策略也有所不同

(1)低危患者

治疗路径:依据指南中PAH患者的治疗流程图,低危患者应采用单药治疗,经过3~6个月治疗之后,如患者仍为低危,则可维持原有治疗方案,并继续进行规律随访。(图1)

治疗方案:无论是内皮素受体拮抗剂、5型磷酸二酯酶抑制剂,还是前列环素类药物,各种药物均可使用,但前列环素类药物通常采用吸入或注射方式使用,应用不便,因此一般建议低危患者以口服药物为主。

图1. 肺动脉高压患者治疗流程图

(2)中危患者

治疗路径:中危患者的治疗,仍存在部分争议。指南建议,中危患者采用初始口服联合治疗;对于小部分特殊情况的患者,比如高龄,家庭经济条件较差,或长期采用药物治疗且病情非常稳定患者等,可继续采用单药治疗。3~6个月随访后,如仍为中危,应采用强化治疗,包括增加药物剂量、增加联合治疗药物种类,以便患者危险级别降至低危。(图1)

治疗方案:无论是内皮素受体拮抗剂,还是5型磷酸二酯酶抑制剂,组合方案有很多种,目前唯一一个有较好循证医学证据证实的方案是,安立生坦+他达拉非联合治疗。AMBITION研究为首个PAH初始联合治疗RCT研究,该研究显示联合治疗组(安立生坦+他达拉非)首次临床失败事件发生时间迟于安立生坦或他达拉非单药治疗(18% vs 31%,风险比0.5,P<0.001),为临床医师对中危患者联合用药治疗提供了信心。

(3)高危患者

治疗路径:临床中,高危PAH患者更为常见,此类患者治疗更加棘手。指南建议首先采用初始联合药物治疗,且治疗药物中必须包括经静脉或皮下注射的前列环素类药物,该类药物为目前国内PAH治疗最强的靶向药物;3~6个月随访后,仍为高危,则应采取强化治疗。(图1)

治疗方案:首先应积极对其进行抗右室心力衰竭(右心衰)治疗,包括氧疗、抗凝治疗、容量管理(补液和利尿剂治疗)、地高辛治疗、血管活性药物(肾上腺素、去甲肾上腺素、多巴胺和多巴胺丁胺、左西孟旦)治疗、PAH靶向药物治疗等。需要指出的是,容量管理非常重要,尽管当前许多临床医师对于容量管理非常重视,比如大剂量使用利尿剂,但这样治疗将对患者的血流动力学带来非常不利影响;强心药物地高辛可改善症状,但不改善预后。

高危患者之容量管理

绝大多数患者右室充盈压升高及心排量低,补液会导致右室充盈压进一步升高、室间隔左移、三尖瓣返流加重、左室充盈减少,此时应加强利尿。但在少数情况下,给予患者大剂量利尿剂治疗,患者反而可能会出现有效循环血容量不足,此时适当补液是合理的。因此,临床医师应耐心细致地评估患者容量是否足够,如不足,可给予患者补液治疗并进行观察,如容量过多,应积极加强利尿和强心治疗。

利尿剂在重症PAH中的应用:

口服利尿剂建议以袢利尿剂为主,袢利尿剂为一线用药,利尿效果较好,可有效降低循环血容量,病情严重时,可短期应用静脉利尿剂,一旦改善应及时改为口服用药;

小剂量多巴胺(100~200 ug/分钟)可增强或改善利尿剂的利尿效应;

新型利尿剂,如重组人脑利钠肽(新活素)、托伐普坦也可在重症PAH患者中使用。

当然,除左右心室内不同乳头肌起源的室速需要相互鉴别外,此类患者还需要与其他亚类的室速,如起源于左前分支者相鉴别。作为传导系统的终末分支,浦肯野纤维覆盖心室内膜面,主要分布于心室中部区域并围绕复杂排列的乳头肌

高危患者之血管活性药物的使用

国际指南更推荐多巴酚丁胺和多巴胺。

多巴酚丁胺:(小剂量,<5 ug/kg/min)可增加心排量、降低肺血管阻力,且有大规模临床研究证据支持,因此,该药物是国外用于右心衰治疗最为常用的药物;

多巴胺:(2.5~5 ug/kg/min)也有同样的效果,可增加心排量、对于肺血管阻力影响不明确,但其最大好处在于可增加肾脏血流,从而增强其利尿效果;

左西孟旦:同样具有降低肺血管阻力作用,同时还可降低体循环阻力,对于第2大类左心肌酶相关的PAH患者治疗效果较好;

去甲肾上腺素:可增加心排量、增加体循环阻力,也有大规模临床试验的证据支持,临床上也具有一定效果。

因此,临床上应根据不同的情况选择不同的血管活性药物。

血压偏低且心率无明显增快可选用多巴酚丁胺和/或多巴胺;

去甲肾上腺素不作为单独治疗药物,如采用较大剂量多巴酚丁胺或多巴胺,仍合并低血压时可考虑联合应用去甲肾上腺素;

血压低且心率明显减慢时,可应用肾上腺素,兼有去甲肾上腺素和多巴酚丁胺的优点,但有导致乳酸贮积及心肌缺血的可能;

左西孟旦可Ca2+浓度依赖性地结合TnC,增强心肌收缩力,也可激活ATP敏感性K+通道扩张血管,改善血流动力学。

总 结

肺动脉高压危险分层是制定治疗策略的基础。对于初诊为中危的肺动脉高压患者建议以口服起始联合治疗为主;如随访仍为中危,建议启动以前列环素为基础的联合治疗。对于高危肺动脉高压患者,建议首先积极纠正右室心力衰竭,合理使用利尿剂和血管活性药物,并给予以前列环素类药物为基础的联合治疗。此外,对于高危、进展迅速或其他靶向药物治疗失败的PAH患者,可采用目前国内最强的PAH靶向药物瑞莫杜林。

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    2021-06-05 ms8000000764578948

    学习了

    0

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    2021-05-24 ms9000000107687138

    好好,学习了

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1720528, encodeId=52ef1e2052802, content=<a href='/topic/show?id=09bf36e741d' target=_blank style='color:#2F92EE;'>#危险分层#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36774, encryptionId=09bf36e741d, topicName=危险分层)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1d5032846700, createdName=tidiq, createdTime=Tue Dec 15 08:27:57 CST 2020, time=2020-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925367, encodeId=f952192536edd, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Oct 13 21:27:57 CST 2021, time=2021-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971053, encodeId=87589e1053ed, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=140, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56ef5464082, createdName=ms8000000764578948, createdTime=Sat Jun 05 09:08:34 CST 2021, time=2021-06-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=968247, encodeId=c85596824ecb, content=好好,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=119, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cbef5482049, createdName=ms9000000107687138, createdTime=Mon May 24 21:55:24 CST 2021, time=2021-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050911, encodeId=473910509110c, content=肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Sun Nov 08 00:27:57 CST 2020, time=2020-11-08, status=1, ipAttribution=)]
    2020-11-08 明天jing

    肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。

    0

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