CHC 2014:许顶立谈心衰患者利尿剂抵抗的问题

2014-08-13 小田 整理 医学论坛网

在9日的中国心脏大会(CHC2014)会上,南方医科大学南方医院许顶立教授介绍了心力衰竭(以下简称心衰)患者利尿剂抵抗的相关知识。 已有研究表明,袢利尿剂是治疗心衰患者充血的主要利尿药物,因此心衰患者“利尿剂抵抗”和心肾综合征的防治十分重要。 利尿剂抵抗定义 发表于2007年《中华心血管病杂志》的一项研究显示,心衰进展和恶化时常需加大利尿剂剂量,最终再大剂量亦无反应时,即出现

在9日的中国心脏大会(CHC2014)会上,南方医科大学南方医院许顶立教授介绍了心力衰竭(以下简称心衰)患者利尿剂抵抗的相关知识。


已有研究表明,袢利尿剂是治疗心衰患者充血的主要利尿药物,因此心衰患者“利尿剂抵抗”和心肾综合征的防治十分重要。

利尿剂抵抗定义

发表于2007年《中华心血管病杂志》的一项研究显示,心衰进展和恶化时常需加大利尿剂剂量,最终再大剂量亦无反应时,即出现利尿剂抵抗。另有定义为,在急性失代偿性心力衰竭(ADHF)患者中,尽管利尿剂剂量递增,但仍无法充分控制水钠潴留时则被称为“利尿剂抵抗”,常出现在有高死亡率危险的ADHF亚组人群中。

2001年美国心脏病学学会/美国心脏学会(ACC/AHA)认为,需特殊干预治疗的难治性心衰(因心衰频繁住院治疗且不能从医院安全出院者、等待心脏移植者、在家中接受静脉支持治疗者、正在使用机械循环辅助装置者和在重症病房接受心衰治疗者等)均可归结于“利尿剂抵抗”。

造成利尿剂抵抗的可能原因

一、利尿剂剂量不足

袢利尿剂是“阈药物”,只有超过“阈剂量”才能达到治疗效果,而心衰患者较健康人群的“阈剂量”明显提高。在心衰患者中观察到的剂量效应曲线变化表明,剂量不足是心衰患者缺乏利尿反应的常见原因。临床上区分利尿剂抵抗与剂量不足是公认的难题,也是目前亟待研究的一个领域。一般认为,袢利尿剂剂量增加超过已知上限剂量或接近每日推荐剂量的最大量(如呋塞米120—160 mmHg)而无改善利尿,才表明利尿剂抵抗。

二、肾脏利钠反应的“制动现象”

长期应用袢利尿剂常导致利钠反应减弱,这种现象常是由于细胞外液量相对或绝对减少,通过RAAS和交感神经介导的机制减少溶质向近端肾小管的运输,同时通过自适应上皮肥大和机能亢进增强远端肾单位的溶质重吸收所致。因此,应尽可能避免大剂量袢利尿剂长期应用。

三、利尿后钠潴留或“反跳”

当肾小管液中袢利尿剂药物浓度低于治疗水平,即会有利尿后钠潴留或“反跳”期。袢利尿剂给药次数不合适也可导致大量利尿后的钠潴留发生,尤其在未限制饮食中钠摄入患者更常见。因此,通过一日多次或连续输注袢利尿剂来限制这种“反跳”效果时,袢利尿剂常会更有效。

防治策略:

一、增加袢利尿剂剂量:在使用常用剂量(如呋塞米20—40mmHg/d)效果不佳时,可在严密监测肾功能和电解质情况下根据临床情况增加利尿剂剂量,应用过程中应监测尿量,并根据尿量和症状改善情况调整剂量。

二、静脉推注联合持续静脉滴注:静脉持续和多次应用可避免因利尿剂浓度下降引起的钠水重吸收。

三、注意同时纠正低氧、酸中毒、低钠和低钾等,尤其注意避免和纠正低血容量状态。

四、噻嗪类利尿剂可有效辅助袢利尿剂:噻嗪类利尿剂常在应用袢利尿剂1小时前口服给药,这种方案可有效克服利尿剂抵抗,但需严密监测体液状态和血电解质,防止引起严重血容量不足或电解质紊乱(低钾血症和低镁血症)而增加心律失常风险。

五、使用能产生利钠效果剂量的醛固酮拮抗剂:这是克服利尿剂抵抗的另一种方法。虽然这些药物属于利尿剂,但其标准剂量对慢性心衰患者的利尿作用有限,较大剂量螺内酯可辅助袢利尿剂实现利钠作用。由于袢利尿剂可引起RAAS系统激活加剧和继发性醛固酮增多症,醛固酮潴钠作用的抑制可增强利钠。但由于这种方法安全性数据有限,使用时需非常谨慎并密切监测容量状态和电解质,避免高血钾。

六、改用或联用血管加压素V2受体阻断剂托伐普坦:临床试验证明了其安全性和有效性,具有排水不利钠的作用,对顽固性水肿或低钠血症患者疗效更显著。推荐用于心衰患者常规利尿剂治疗效果不佳、有低钠血症或肾功能损害倾向患者应用,可显著增加尿量和改善充血相关症状。

七、将高渗盐水(HSS)或白蛋白与袢利尿剂短期混合应用:已有几项针对上述方法的试验取得了积极的研究结果。低容量HSS或白蛋白有益的假设机制包括改善神经激素抑制和肾脏血流,从而恢复有效动脉容量和增强利尿剂的反应性,但鉴于ADHF患者机体总钠量过多,使用这种抑制机体不良反应和促进利尿疗效的治疗方案还需更为谨慎的对照试验来验证。

八、小剂量奈西立肽、小剂量多巴胺分别与袢利尿剂联合用药问题:早期研究表明,小剂量多巴胺增加稳定性心衰患者的肾小球滤过率和肾血流量,而对ADHF伴有肾功能不全患者给予小剂量奈西立肽、小剂量多巴胺分别与袢利尿剂联合应用是否增加尿量和改善肾功能,2013年发表的急性心衰肾脏优化治疗评估(ROSE-AHF)研究进行了解答——ROSE-AHF研究结论阴性。

    ROSE-AHF研究亚组分析显示,小剂量奈西立肽与袢利尿剂联用可能增加左室射血分数(LVEF)<50%或收缩压<114 mmHg心衰患者的尿量,可能有益;小剂量多巴胺与袢利尿剂联用可能减少LVEF>50%心衰患者的尿量,可能有害。

九、超滤治疗:不同形式的超滤治疗在难治性水肿中已应用了几十年,近来外周静脉-静脉超滤成为利尿剂抵抗心衰患者替代袢利尿剂治疗ADHF的有效方法。一些学者认为,只有患者符合以下两个条件即可用血液净化治疗:1、急性心衰伴高血容量;2、血肌酐≥1.5 mg/dl或口服呋塞米80 mg无效。

    但使用该方法时须注意以下几点:1、血管内容量移除率不能超过毛细血管再充盈率,因为这可能导致RAAS进一步激活、低血压和肾损伤;2、无论是住院或门诊患者,反复超滤的获益并不明确;3、对于静脉通路不佳、血液高凝状态、低血压、晚期肾脏疾病、心源性休克和那些需变力性药物维持的患者,一般不适用于超滤治疗。因此,目前指南推荐,超滤治疗仅用于对初始药物治疗无反应的患者(Ⅱa类,证据级别:B)。

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  1. [GetPortalCommentsPageByObjectIdResponse(id=338785, encodeId=3609338e85c6, content=文章很好非常棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/TNV5cElot3tDNlyIMGic8HtYGcKD9cIvZR1TXRasIwjyib9BdYd3p4jcM75yvkr22FDhd6jseJmBOLaGyejic1vew/132, createdBy=fc402371135, createdName=润泽River, createdTime=Wed Aug 15 15:16:32 CST 2018, time=2018-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=34323, encodeId=3ee134323c8, content=治疗他们不容易, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3ykRSkuxjt93yc9tvDWfIQItrwiaKSCps5kyrTyDlwic2FgoCWe88wR3ZiaggKYGueDIp26zVgnbzriaQ/0, createdBy=89d71602869, createdName=sundong, createdTime=Tue Aug 04 08:23:00 CST 2015, time=2015-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007251, encodeId=34ed200e2513b, content=<a href='/topic/show?id=b34b9138164' target=_blank style='color:#2F92EE;'>#许顶立#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91381, encryptionId=b34b9138164, topicName=许顶立)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Tue Oct 28 05:39:00 CST 2014, time=2014-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271924, encodeId=040d12e192451, content=<a href='/topic/show?id=573332291bd' target=_blank style='color:#2F92EE;'>#利尿剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32291, encryptionId=573332291bd, topicName=利尿剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca89104, createdName=huperzia, createdTime=Fri Aug 15 00:39:00 CST 2014, time=2014-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373273, encodeId=6ef413e3273b8, content=<a href='/topic/show?id=2fd051939ab' target=_blank style='color:#2F92EE;'>#心衰患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=51939, encryptionId=2fd051939ab, topicName=心衰患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=467c360, createdName=yuanming7, createdTime=Fri Aug 15 00:39:00 CST 2014, time=2014-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1552110, encodeId=afe5155211075, content=<a href='/topic/show?id=2d194589f3' target=_blank style='color:#2F92EE;'>#CHC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4589, encryptionId=2d194589f3, topicName=CHC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0cbf14265668, createdName=mei536, createdTime=Fri Aug 15 00:39:00 CST 2014, time=2014-08-15, status=1, ipAttribution=)]
    2018-08-15 润泽River

    文章很好非常棒

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    2015-08-04 sundong

    治疗他们不容易

    0

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    2014-08-15 mei536