先天性心脏病相关性肺动脉高压诊治专家共识(下）

六、预后

预后较简单分流性CHD差，如不早期干预，仅有少数患者能存活至成年。预后与心脏畸形复杂程度和治疗时机密切相关（见表6）。单纯分流畸形，婴幼儿期外科解剖矫治术较好，严重PAH阶段则预后欠佳，成人患者即使手术也预后不佳。

表6.常见复杂先天性心脏病相关性肺动脉高压的分类及预后（非ES期）

疾病名称	诊断方法	主要分流水平	最佳手术时间	手术方式	预后
完全性房室隔缺损	UCG/RHC	房、室水平	3-12个月	缺损修补＋瓣膜成形/Banding术	较好
永存动脉干	Angio/RHC	肺动脉、室水平	2-3个月	修补VSD，带瓣管道重建肺动脉－右室通道	一般外管道晚期需更换
无肺窄的单心室	Angio/RHC	房、室水平	3-12个月	方坦类手术/Banding术	一般，难以解剖矫治
无肺窄的大动脉转位合并VSD	Angio/RHC	室水平	3-12个月	动脉调转手术	一般，解剖矫治难度大
右室双出口（Taussing-Ping畸形）	Angio/RHC	室水平	1-3个月	动脉调转＋VSD修补/Banding术	一般
主肺间隔缺损	UCG/RHC	肺动脉水平	3-12个月	体外循环下修补/介入治疗	良好
主动脉弓离断	CT、MRI/ RHC	肺动脉、室水平	3-12个月	一期解剖根治	良好

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第五节 围手术期相关性的肺高压

PH可发生于CHD演变过程中的各个阶段，是决定手术时机、手术方式的重要因素之一。手术创伤和体外循环（cardiopulmonary bypass，CPB）会诱发全身炎性反应综合征，导致肺血管内皮细胞受损，血栓素A2、ET-1等缩血管的细胞因子增多，PVR增高，诱发 PAH[67]。

一、术后反应性肺高压和肺高压危象

先天性体循环至肺循环分流相关性PAH患者术后ET-1下降至正常水平需要48h左右[68,69]。这些患者大多术前PVR已经升高，加上手术创伤和 CPB影响，术后早期（＜30d）PAP高于正常，称为术后反应性肺高压（reactive pulmonary hypertension，RPH）[70]。术后RPH以及肺高压危象（pulmonary hypertension crisis，PHC）是CHD术后早期常见并发症及死亡原因[71,72]。随着手术技术和治疗方法的改进，RPH和PHC的发生率由上世纪八十年代的 31％降至上世纪九十年代的6.8％；同时，死亡率由71％降至29％。近期报道显示致命性PH及PH危象已明显减少，发生率分别为2％和0.7％，但完 全性房室间隔缺损伴Down’s综合征发生率仍偏高。

二、临床表现

RPH  PAP增高，严重者可出现右心衰竭，表现为颈静脉怒张，肝脏增大，腹水，腹壁静脉显露，尿量减少，听诊肺动脉第二音亢进。

PHC  系PAP迅速上升，达到或超过体循环压力，导致CO和SaO2明显下降所致。一旦出现PHC, 临床症状急剧恶化，表现为严重低心输出量综合征。SaO2下降，高碳酸血症，代谢性酸中毒，患儿出现紫绀[73]。听诊肺动脉第二音亢进，心脏杂音变轻。

三、诊断

1．诊断标准

术后RPH  海平面安静状态时mPAP≥25mmHg。

PHC   PAP急剧升高，超过体动脉压力，伴或不伴有体动脉压力下降；CO和SaO2明显下降。

2.术前高危因素

（1）年龄(按病种分类) :＞6 m（TGA/TAPVC/PTA/IAA/SV），＞1 y（CAVC/DORV），＞2 y（VSD/PDA），＞4 y（ASD）。

（2）临床表现  :呼吸道感染减少，伴心功能（活动量）降低；渐进性青紫，SaO2＜95％(不吸氧时)。

（3）辅助检查 :胸部X线  心影缩小，肺动脉段突出。

心电图  电轴右偏，右心室肥厚。

超声心动图  心室、心房、大血管水平双向分流，以右向左分流为主。

肺小动脉造影  肺动脉分支管径细且不齐，末梢蜷曲，毛细血管充盈差。

心导管检查  Pp/Ps＞0.75，Qp/Qs＜2，PVR＞9woods，PWP＜12mmHg[7]。

3.确诊

    虽然心导管检查是指导制定科学治疗方案的重要手段，但由于心导管检查操作的危险性和条件要求，临床上大多用无创手段来评估mPAP。根据中华医学会小儿外 科学分会胸心外科学组制定的各类CHD手术安全无创评估方法[74]，在无创评估中，需双心室修补的患儿得分＞8分、单心室修补的患儿＞6分为外科手术高 危人群，这类患儿在围术期较易出现RPH和PHC，推荐术前行心导管检查。双心室修补的患儿，心导管检查得分≤4分可行外科根治术，5-7分可由外科医师 决定行姑息术或根治术，在外科手术中需进行必要的技术处理，如保留心房水平分流，VSD补片上行单向开孔活瓣等。鉴于经过PAH靶向治疗后PVR持续下 降，从而获得手术指征并成功实施修补术的报道少见[75,76]，心导管检查得分≥8分的患儿不建议行根治手术治疗。单心室修补的患儿由于最终拟实现 Fontan循环，正常甚至低于正常的PVR是手术成功关键，故心导管评分≤4分的患儿若≤6个月可随访观察，＞6个月可行BCPS手术或TCPC术。 5-7分患儿建议行肺动脉环缩术，术后每3个月随访1次，根据随访结果决定是否需行BCPS术或TCPC术，＞8分的患儿暂不考虑BCPS术或TCPC 术。

1     四、治疗

术后RPH和PHC重在预防，预防方法见表7。治疗主要包括支持疗法、选择性肺血管扩张剂和联合治疗等。

表7. 反应性肺高压和肺高压危象预防策略

1．支持治疗

（1）解剖因素  如存在明显残余分流、残余梗阻、瓣膜反流，必要时再次手术纠治。PHC时保留心房水平右向左分流可维持一部分心排血量。

（2）镇静、镇痛、松弛肌肉  术后2-3d内保持患者绝对安静，在机械通气中除常规应用咪唑安定、万可松等镇静剂与肌松剂外，芬太尼或舒芬太尼持续静脉给药 (0.5-2 ug /kg/h) 亦是有效措施之一。

（3）机械通气   PH患者术后机械通气需要维持48-72h，通常应维持适当过度通气和良好的氧合，但也不能过分追求过度通气，大潮气量可引起机械通气相关肺损伤。呼气末正压（positive end expiratory pressure，PEEP）对改善氧合，防止肺不张发生十分重要，常规设定压力4～6cm水柱以防止肺泡萎陷。

（4）碱化血液  酸中毒是一种潜在的肺血管收缩剂。机械通气不良，伴酸中毒或高碳酸血症会增加PVR。血pH值＜7.31，PaCO₂＞53 mmHg，PVR将增加2倍以上。反之，机械通气至血pH值≥7.5，可降低婴儿PVR。至关重要的是，机械通气期间，血pH值是影响PVR的有效因素，而非PaCO₂。临床上可通过碱化血液（静脉推注5％碳酸氢钠 2ml/kg/次），将血pH值维持在pH值7.45-7.55之间以降低PVR。

（5）最佳血细胞比容 血细胞比容对PVR影响大于体循环阻力，一般维持血细胞比容35％-45％。

（6）正性肌力药物支持   氨力农和米力农是CHD术后应用较广的正性药物，兼有扩张血管和舒张心室作用。氨力农半衰期2-4h，但对肝、肾具有毒副作用。米力农优点为半衰期短，对PH和低心排患者，比高剂量儿茶酚胺有明显优势，可增加心指数，降低PAP、心房压力以及心肌氧耗量。

2.肺血管扩张剂

因负性肌力作用和体循环阻力下降可加重病情，CCB不推荐用于儿科病例。其他传统的血管扩张剂如妥拉唑啉、苯氧苄胺（酚苄明）、硝普钠、异丙基肾上腺素、前列腺素E₁等，因缺乏肺血管选择性，临床已不作为一线治疗药物。对于体-肺分流相关性PAH，针对不同发病环节的特异性肺血管扩张剂只有少量随机对照试验报道^[77-82]，对于这类患者的治疗更多取决于专家经验^[83] ，常见使用药物见表8。

表8.治疗反应性肺高压和肺高压危象常用血管扩张剂

     3.注意事项

对于存在肺静脉回流梗阻或左心室功能不全患儿，禁止使用NO、伊洛前列素等急性肺血管扩张剂，推荐使用起效相对缓慢的肺血管扩张剂，如ET受体拮抗剂和PDE-5抑制剂等，使左心房有充分时间接纳来自肺静脉回流的血液。对于主动脉缩窄、主动脉弓中断合并VSD者，因术前存在体-肺分流引起的肺充血和左心梗阻引起的肺淤血性PH，早期PVR就可能明显升高，术后仍可存在PH。由于左心系统发育不良可能小，术后仍可应用伊洛前列素、NO等急性肺血管扩张剂。

{nextpage} 第六节 术后迟发性肺动脉高压

迟发性PAH是相对于术后RPH而言，这类患者因术前即存在重度PAH，术后虽然无PHC发生，但PAP未完全降至正常，经过一段时间后PAH再次加重而 出现右心衰竭症状。因此，真正意义上的迟发性PAH并不存在，应称之为术后持续性PAH更为合适。即使极少数患者术后PAP完全降至正常然后再发生 PAH，也可能与术前PAH关系不大，而是IPAH表现。因临床习惯，本共识仍称之为迟发性PAH。对于术后迟发PAH如何界定，目前并不明确，鉴于部分 患者术后RPH的存在，本共识认为，以术后6个月mPAP仍然高于25mmHg作为术后迟发PAH时间界限较为合适。

一、发生率

外科修复术后迟发PAH发生率，现有统计资料较少。注册研究显示，间隔缺损矫正手术后PAH发生率为2％-3％，VSD关闭术后PAH发生率约2％，继发孔ASD术后发生率约3％[2,64,84]。

二、临床类型

临床对CHD术后迟发性肺高压了解不多，与术后RPH的区别在于，虽然成功渡过术后早期阶段（≥6个月），但PAH继续发展或持续存在。根据手术方式，可分为两种：

1.完全矫正术后  指CHD外科矫治术后PAH，可在术后即刻、几个月或几年后出现PAH，同时没有残余分流或与外科手术相关的后遗症。

2.不完全矫正术后  包括功能性单心室行BCPS和TCPC术后。

三、致病因素

肺血管床功能和结构状况是决定患者症状和预后的关键因素。术后迟发性PAH可能与手术时机过迟、误判手术可能性、右心室后负荷长期作用导致结构重塑不可逆 转等有关。CHD患者可能还隐藏有造成PAH的其他多种因素，包括长期体循环后负荷增加使左心室肥厚、左侧房室舒张功能不全、瓣膜异常、肺静脉高压或梗 阻。主要致病因素包括以下几种：

1.与外科手术相关的危险因素  缺氧、酸中毒、刺激交感神经和手术牵拉，均可导致肺血管阻力增加；过度通气和肺不张也可增加肺血管阻力；术后采用PEEP较大时，PVR增加，但中度 PEEP可逆转肺水肿和肺不张，降低PVR；适当过度通气将血液pH值提高到7.5，可降低婴儿PVR。

 2.与麻醉相关的危险因素  虽然个体反应不同，一些麻醉药也可影响肺循环阻力。早期报道氯胺酮可增加肺血管阻力，但只要保持正常通气则不会增加肺血管阻力[4]。

 3.与体外循环相关的因素  CPB可以引起肺血管内皮功能紊乱，肺循环阻力增高。

 4.与介入治疗相关的因素  导管操作不当导致肺血管损伤；由于渗透压高于血浆，或者粘度较高，造影剂可损伤肺血管内皮细胞，加重PAH 病情。

四、预后

预后很差，预期寿命甚至短于未手术的CCHD和ES患者，较ES患者累计生存时间短，平均为1.3年。

五、治疗

参见第一章第八节先天性心脏病相关性肺动脉高压的治疗。

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