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Article(id=1199335050086019743, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199335049175859209, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.1016.2023.1228, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1691942400000, receivedDateStr=2023-08-14, revisedDate=null, revisedDateStr=null, acceptedDate=1697731200000, acceptedDateStr=2023-10-20, onlineDate=1763873358508, onlineDateStr=2025-11-23, pubDate=1711555200000, pubDateStr=2024-03-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763873358508, onlineIssueDateStr=2025-11-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763873358508, creator=13701087609, updateTime=1763873358508, updator=13701087609, issue=Issue{id=1199335049175859209, tenantId=1146029695717560320, journalId=1189873630562394117, year='2024', volume='49', issue='3', pageStart='245', pageEnd='366', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763873358291, creator=13701087609, updateTime=1763874044185, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1199337926086721596, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199335049175859209, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1199337926086721597, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199335049175859209, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=252, endPage=258, ext={EN=ArticleExt(id=1199335051428197027, articleId=1199335050086019743, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Interpretation of "Extracorporeal Life Support Organization (ELSO): guidelines for neonatal respiratory failure", columnId=1199335049955999755, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Special Issue of Diagnosis and Treatment of Neonatal Respiratory Distress Syndrome, runingTitle=null, highlight=null, articleAbstract=

According to the extracorporeal life support (ECLS) registry report, the use of extracorporeal membrane oxygenation (ECMO) in neonates with severe respiratory failure reached its peak in 1992. With the emergence of new respiratory support methods such as nitric oxide, pulmonary surfactant, and high-frequency ventilation, the number of neonates with ECMO for respiratory support decreased gradually, maintaining at about 1000 cases per year. However, it also means that the neonates who need ECMO support will be in a more severe condition, which requires higher requirements for clinicians. In order to further standardize the technique of neonatal extracorporeal life support, the Extracorporeal Life Support Organization (ELSO) published the guidelines for neonatal respiratory failure in 2020. The guidelines provide suggestions on the technology, patient management and complications during ECMO. This article mainly interprets the patient selection, support mode, technical considerations, management and complications during ECMO.

, correspAuthors=Xiao-Yang Hong, authorNote=null, correspAuthorsNote=
E-mail:
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根据体外生命支持系统(ECLS)注册报告，体外膜肺氧合(ECMO)在新生儿严重呼吸衰竭支持的应用在全球于1992年达到顶峰。随着一氧化氮、肺表面活性物质的应用，以及高频通气等新型呼吸支持手段的出现，采用ECMO支持新生儿呼吸的病例数量逐渐减少，维持在约1000例/年。但这意味着需要ECMO支持的新生儿病情将会更重，对临床医师的要求更高。为了进一步规范新生儿体外生命支持技术，体外生命支持组织在2020年发布了新生儿呼吸衰竭的指南。指南对ECMO期间的技术、患儿管理及并发症处理等提出了建议，本文主要从患儿选择、支持模式、技术考虑、ECMO期间的管理及并发症处理等方面进行解读。

, correspAuthors=洪小杨, authorNote=null, correspAuthorsNote=
洪小杨，E-mail：
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冯秋霜，硕士研究生，主要从事儿科体外生命支持的临床与基础研究

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VV ECMO. 静脉-静脉体外膜肺氧合；VA ECMO. 静脉-动脉体外膜肺氧合；SvO2. 混合静脉血氧饱和度；SpO2. 经皮氧饱和度；PaO2. 动脉血氧分压；PaCO2. 动脉血二氧化碳分压

, figureFileSmall=JfQcQrR5two97KOFhtFLHA==, figureFileBig=Cx1A1PazU/E4Xyk5wsntbw==, tableContent=null), ArticleFig(id=1199352815358411241, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1199335050086019743, language=EN, label=Tab.1, caption=

Anticoagulation monitoring

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指标正常范围影响因素
ACTACT的目标为正常值的1.5倍肝素，凝血因子，血小板水平，感染和体温
PTT正常范围与年龄有关，新生儿值更高。目标是正常的1.5倍肝素，凝血因子，AT Ⅲ水平。如果FⅧ升高，APTT可能会低估抗凝作用
血浆抗Xa抗Xa水平建议维持在0.3~0.7 U/ml高脂血症、溶血和高胆红素血症。一些实验室将外源性AT Ⅲ添加到抗Xa检测中，这可能会影响结果，特别是在内源性AT Ⅲ水平较低的新生儿中
TEG测量有无肝素作用可能有助于区分潜在的凝血病。手术出血，肝素所致出血
AT Ⅲ目标是正常值的80%~120%。生理情况下，新生儿AT Ⅲ血浆浓度偏低，约为成人值的60%。低AT Ⅲ水平可通过给予新鲜冷冻血浆或重组AT Ⅲ治疗低AT Ⅲ导致肝素抵抗和血栓形成
血小板减少症ECMO期间，维持在5万~10万/ml，具体取决于各ECMO中心的实际情况
纤维蛋白原对于出血患儿，通过输注新鲜冷冻血浆或冷沉淀，使纤维蛋白原维持至>1.5 g/L，普通患儿维持至>1.0 g/L当存在血凝块时，可能会导致其耗尽
), ArticleFig(id=1199352815572320749, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1199335050086019743, language=CN, label=表1, caption=

ECMO的抗凝监测

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指标正常范围影响因素
ACTACT的目标为正常值的1.5倍肝素，凝血因子，血小板水平，感染和体温
PTT正常范围与年龄有关，新生儿值更高。目标是正常的1.5倍肝素，凝血因子，AT Ⅲ水平。如果FⅧ升高，APTT可能会低估抗凝作用
血浆抗Xa抗Xa水平建议维持在0.3~0.7 U/ml高脂血症、溶血和高胆红素血症。一些实验室将外源性AT Ⅲ添加到抗Xa检测中，这可能会影响结果，特别是在内源性AT Ⅲ水平较低的新生儿中
TEG测量有无肝素作用可能有助于区分潜在的凝血病。手术出血，肝素所致出血
AT Ⅲ目标是正常值的80%~120%。生理情况下，新生儿AT Ⅲ血浆浓度偏低，约为成人值的60%。低AT Ⅲ水平可通过给予新鲜冷冻血浆或重组AT Ⅲ治疗低AT Ⅲ导致肝素抵抗和血栓形成
血小板减少症ECMO期间，维持在5万~10万/ml，具体取决于各ECMO中心的实际情况
纤维蛋白原对于出血患儿，通过输注新鲜冷冻血浆或冷沉淀，使纤维蛋白原维持至>1.5 g/L，普通患儿维持至>1.0 g/L当存在血凝块时，可能会导致其耗尽
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体外生命支持组织(ELSO)：新生儿呼吸衰竭指南解读
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冯秋霜 1, 2 , 洪小杨 1, 2, *
解放军医学杂志 | 新生儿ARDS诊断与治疗专题 2024,49(3): 252-258
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解放军医学杂志 | 新生儿ARDS诊断与治疗专题 2024, 49(3): 252-258
体外生命支持组织(ELSO)：新生儿呼吸衰竭指南解读
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冯秋霜1, 2, 洪小杨1, 2, *
作者信息
  • 1南方医科大学第二临床医学院，广东广州 510515
  • 2解放军总医院第七医学中心，北京 100700

    • 冯秋霜，硕士研究生，主要从事儿科体外生命支持的临床与基础研究

通讯作者:

洪小杨，E-mail：
Interpretation of "Extracorporeal Life Support Organization (ELSO): guidelines for neonatal respiratory failure"
Qiu-Shuang Feng1, 2, Xiao-Yang Hong1, 2, *
Affiliations
  • 1Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China
  • 2Seventh Medical Center, Chinese PLA General Hospital, Beijing 100700, China
出版时间: 2024-03-28 doi: 10.11855/j.issn.0577-7402.1016.2023.1228
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摘要
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根据体外生命支持系统(ECLS)注册报告，体外膜肺氧合(ECMO)在新生儿严重呼吸衰竭支持的应用在全球于1992年达到顶峰。随着一氧化氮、肺表面活性物质的应用，以及高频通气等新型呼吸支持手段的出现，采用ECMO支持新生儿呼吸的病例数量逐渐减少，维持在约1000例/年。但这意味着需要ECMO支持的新生儿病情将会更重，对临床医师的要求更高。为了进一步规范新生儿体外生命支持技术，体外生命支持组织在2020年发布了新生儿呼吸衰竭的指南。指南对ECMO期间的技术、患儿管理及并发症处理等提出了建议，本文主要从患儿选择、支持模式、技术考虑、ECMO期间的管理及并发症处理等方面进行解读。

体外膜肺氧合  /  新生儿  /  呼吸衰竭

According to the extracorporeal life support (ECLS) registry report, the use of extracorporeal membrane oxygenation (ECMO) in neonates with severe respiratory failure reached its peak in 1992. With the emergence of new respiratory support methods such as nitric oxide, pulmonary surfactant, and high-frequency ventilation, the number of neonates with ECMO for respiratory support decreased gradually, maintaining at about 1000 cases per year. However, it also means that the neonates who need ECMO support will be in a more severe condition, which requires higher requirements for clinicians. In order to further standardize the technique of neonatal extracorporeal life support, the Extracorporeal Life Support Organization (ELSO) published the guidelines for neonatal respiratory failure in 2020. The guidelines provide suggestions on the technology, patient management and complications during ECMO. This article mainly interprets the patient selection, support mode, technical considerations, management and complications during ECMO.

extracorporeal membrane oxygenation  /  neonate  /  respiratory failure
冯秋霜, 洪小杨. 体外生命支持组织(ELSO)：新生儿呼吸衰竭指南解读. 解放军医学杂志, 2024 , 49 (3) : 252 -258 . DOI: 10.11855/j.issn.0577-7402.1016.2023.1228
Qiu-Shuang Feng, Xiao-Yang Hong. Interpretation of "Extracorporeal Life Support Organization (ELSO): guidelines for neonatal respiratory failure"[J]. Medical Journal of Chinese People’s Liberation Army, 2024 , 49 (3) : 252 -258 . DOI: 10.11855/j.issn.0577-7402.1016.2023.1228
正文
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体外膜肺氧合(extracorporeal membrane oxygenation，ECMO)技术作为新生儿重症领域救治不可或缺的重要组成部分，是救治常规治疗无效的心肺衰竭的高级生命支持技术。为进一步改善新生儿ECMO的预后，2020年体外生命支持组织(Extracorporeal Life Support Organization，ELSO)制定了新生儿呼吸衰竭应用ECMO的指南[1]，但该指南并未对各实践要点进行推荐强度分级，而是对涉及新生儿ECMO期间的技术和管理进行了指导。本文在原指南的基础上，从临床实用性出发，结合新生儿ECMO的国内外研究成果进行解读。
1 患儿选择、支持模式与技术考虑
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对于存在严重呼吸和(或)心力衰竭的新生儿，若病因具有潜在可逆性，且无致死性染色体疾病、严重脑损伤及无法控制的出血等ECMO禁忌证，临床医师可在充分评估适应证后考虑进行体外生命支持治疗。随着ECMO生物材料及凝血相关研究的进步，相对禁忌证对此项技术开展的限制逐渐减弱，对于体重<2 kg[2]、胎龄<34周[3]的患儿能否进行ECMO治疗，仍需各中心谨慎评估。图1列出了新生儿ECMO的适应证、禁忌证和支持模式。
1.1 插管
在新生儿呼吸ECMO中选择静脉-动脉(VA)还是静脉-静脉(VV)支持取决于患儿、外科医师及ECMO中心，局部切开进行VA、VV插管或经皮穿刺VV插管均为合理的选择。但根据2023年4月体外生命支持系统(extracorporeal life support，ECLS)注册库的最新报告，全球近5年新生儿呼吸行VV ECMO支持的比例总体呈下降趋势，从2018年的30.9%下降至2021年的9.1%。一方面是由于适合新生儿双腔插管耗材的短缺，另一方面也是因为新生儿静脉血管内径小造成的插管挑战，使得大部分中心无法开展新生儿VV ECMO支持[4]。
1.1.1 插管技术
在大部分情况下，套管型号的选择是在切开血管后确定的[5]。部分外科医师会在插管前通过床旁超声检查右颈部血管，以评估其大小并指导选择。此外还需考虑可能出现的血管痉挛情况，因此，一般选择直径为血管直径的80%(Fr值除以3.14)的套管。
1.1.1.1 直接切开插管
此种插管方式一般在重症监护室进行，需要保证无菌环境，并配备手术室医护团队。首先进行哪支血管置管取决于外科医师的个人偏好。许多医师更喜欢先进行动脉插管，因为相比静脉，动脉位置较深，如颈动脉。也有人主张，静脉置管较动脉置管深，因此应该先插入静脉导管，以降低脱管风险。此外，还需考虑到动脉插管在放置静脉导管时可能会被阻断，导致动脉血栓形成的风险增加，而这将比静脉血栓更为严重。为避免引发血管痉挛，应尽量减少对血管的直接刺激。如果由于血管过小或血管痉挛而出现插管困难，可在血管近端放置牵引线来辅助插管。对于双腔静脉插管，应当进行X线胸片检查以确认静脉插管头端位置是否在右心房或下腔静脉中。超声心动图也可用于评估导管尖端的位置，尤其是在双腔插管时。股动脉插管不适用于新生儿。
1.1.1.2 经皮穿刺插管
部分ECMO中心已经开始采用经皮插管技术对新生儿进行VV ECMO治疗。此方法通过在超声引导下使用右颈静脉通路，并采用Seldinger技术逐渐扩张血管来实现。在扩张过程和最终插入导丝尖端时，应当使用超声和(或)X线透视来确保导丝的安全定位，以避免对血管和心脏造成损伤。
1.1.2 静脉引流
指南提出，大多数情况下，不需要进一步进行静脉引流，因为适当尺寸的导管可提供足够的支持。如果需要增加额外的静脉引流，通常选择颈静脉头端。如果可能，应该使用10 Fr或12 Fr远端有孔的动脉插管进行头侧引流，因为使用8 Fr的动脉插管可能会导致血栓形成。部分中心常规放置头静脉插管以增加静脉引流量，同时希望以此降低脑出血的发生率[6]，但由于尚缺乏高级别证据，指南并不建议常规进行此操作。而股静脉内径小，引流量通常难以满足要求，也不应在新生儿中使用。对于静脉引流不足的患儿，指南建议行中心插管。
1.2 泵的选择
各中心在新生儿使用滚轴泵和离心泵方面存在差异[5]。婴儿使用滚轴泵时可精确控制流量，但也存在着管路破裂的风险。离心泵能够避免管路破裂出血的情况，但精度较低，并可能导致溶血。溶血与神经损伤、肾损伤和较高的病死率相关。但目前尚缺乏关于新生儿泵类型选择的严格数据，泵的选择多基于各中心的专业知识和偏好[7-10]。
1.3 氧合器的选择
推荐额定流量应超过500 ml/min[5]。
2 ECLS期间的管理
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2.1 氧合
组织的氧合受血流、血红蛋白和氧饱和度的影响。氧供应至少为氧耗量[新生儿为6 ml O2/(kg.min)]的3倍，ECMO启动时通常使用100%吸入气氧浓度(fraction of inspiration O2，FiO2)支持。在VA ECMO中，混合静脉血氧饱和度(SvO2)是终末器官氧供充足的良好指标，目标为0.65~0.80。SvO2的变化可作为VV ECMO运行后的病情趋势判断指标。由于高浓度氧的负面影响，如果发现患儿的动脉血PaO2>100 mmHg，应相应地调整回路流量或膜肺氧流量。
2.2 CO2清除率
CO2清除率由气流量控制。CO2的跨膜肺转移比氧交换更高效，因此ECMO启动后需尽早评估血气值，以避免发生低碳酸血症。气流量初始设定为与血流量相等，并根据血气情况进行调整，使患儿的PaCO2保持在40~45 mmHg。
2.3 抗凝
抗凝可使用肝素或直接凝血酶抑制剂(direct thrombin inhibitor，DTI)[5]。在新生儿中，肝素是最常见的抗凝剂，同时，部分中心已经开始使用DTI，但对于新生儿，使用DTI的治疗经验有限，指南并未对此进行推荐。目前仍未就新生儿呼吸ECMO的最佳抗凝方案达成共识或ELSO推荐，也没有理想的抗凝选择。
2.4 抗凝方案
在插管时，一次性推注普通肝素的剂量为50~100 U/kg，然后进行持续输注。考虑到早产儿发生颅内出血(IVH)的风险增加，指南建议插管时的推注剂量为50 U/kg。
新生儿接受ECMO治疗时，ECMO管路应预先使用100 U肝素/单位浓缩红细胞进行抗凝。肝素的输注速率通常从25~30 U/(kg.h)开始。由于新生儿血浆中AT Ⅲ浓度较低，需警惕“肝素抵抗”的发生，即需要增加肝素剂量以达到基于抗Xa、部分凝血活酶时间(PTT)或活化凝血时间(ACT)的预期抗凝效果时，考虑发生了肝素抵抗[11-12]，而肝素诱导的血小板减少症在新生儿中极为罕见。
DTI(如阿加曲班、比伐卢定)不依赖AT Ⅲ发挥作用，与肝素不同的是，其潜在优势在于抑制凝血块与凝血酶的结合。DTI的剂量可通过PTT(1.5~2.0倍正常值)或ACT滴定来确定。如果患儿在开始ECMO前PTT水平异常，可能难以监测DTI对抗凝的影响。此外，随着时间的推移，PTT水平趋于平稳，将导致结果不可靠。抗凝监测方案见表1。
2.5 患儿管理
2.5.1 ECMO支持期间的血流动力学
VV ECMO支持期间，由于患儿需要依靠自身心输出量来维持血流动力学状态，因此，恰当地使用血管活性药物和液体输注以维持心输出量、血压和血管阻力至关重要[5]。虽然VV ECMO回路本身并不提供直接的血压支持，但通常情况下，在进行ECMO之前接受过正性肌力药物支持的患儿，ECMO运行后此类药物的使用将大幅减少。
VA ECMO支持期间，循环将由泵流量、自身心输出量和血管阻力共同控制。由于脉压降低，平均体循环动脉压会稍微低于正常水平。此外，接受心脏支持的患儿在ECMO启动前，由于存在严重心功能不全，通常会使用大剂量正性肌力药物以维持循环灌注。当这些药物浓度降低时，可导致血管阻力降低，从而使体循环压力相应降低。如果全身组织灌注不足，主要表现为尿量减少和灌注不良，此时可通过增加泵流量、输注血制品和(或)滴定血管活性药物来提高动脉压力。在感染性休克患儿中，常使用升压药物使全身血管收缩来实现升压。
SvO2是全身灌注的良好测量指标。在VV ECMO中，由于再循环现象的存在，从ECMO回路中测得的SvO2值是不准确的。部分医疗机构尝试通过关闭ECMO循环30 s，在随后的10 s内测量SvO2来获得准确的测量值，但并无相关研究证明其有效性。如果患儿有头侧引流管，也可在此放置单独的氧饱和探头，以连续监测脑SvO2。指南提出，即使伴有低血压，但若动脉血氧饱和度(SaO2)>0.95，SvO2>0.65依然提示全身氧合充分。如果全身氧供不足(SvO2<0.65)，则可通过增加泵流量，直到灌注充分为止[5]。在VA ECMO中，增加ECMO流量可增加全身的血氧供应。如果需要增加额外的血容量以提高流量，则可考虑输注血制品和晶体溶液。
在VV ECMO情况下，流量变化并不直接影响氧合，因为可能会发生再循环现象。再循环取决于插管位置、患儿容量状态(右心房内径)、自身心功能和流量，临床医师应考虑增加ECMO流量是否能使患儿SaO2升高。增加回路流量可能会加剧再循环现象，表现为SpO2降低和SvO2升高。在这种情况下，应完善X线胸片或超声心动图以评估插管的位置。对于再循环现象的潜在治疗方法包括镇静、调整患儿体位、调整插管位置、合理管理容量及减少回路流量等措施。
2.5.2 呼吸机管理
当ECMO稳定时，无论是VV模式还是VA模式，都应下调呼吸机参数，使肺保持在“休息”状态，最大吸气压(PIP)为15~20 cmH2O，呼气末正压(PEEP)为5~10 cmH2O(在气胸时应更低)，呼吸频率为12~20次/min，吸气时间为0.5~1.0 s，氧浓度(FiO2)为0.21~0.30[5]。患儿动脉血气反映了经ECMO循环，膜肺氧合后的血液(即氧饱和度1.00、二氧化碳分压处于正常范围)与机体静脉回流血液的综合情况。撤机时：(1)对于VV模式，将呼吸机设置从“休息设置”增加到可接受的基线设置，断开膜肺氧气源，如果肺功能在1 h或更长时间内能保持正常，则可考虑对患儿进行撤ECMO操作；(2)对于VA模式，降低流量至100 ml/min，将呼吸机从“休息设置”增加到可接受的基线设置，如果患儿呼吸机FiO2<0.5，血压稳定，通气可接受，则可准备撤ECMO操作。
2.5.3 液体管理
为保证新生儿ECMO回路在运行时血容量的稳定，应预充红细胞以维持血容量和液体平衡。液体管理的目标为使细胞外液量恢复到正常水平(干体重)。在体外循环早期的急性炎症阶段，可能会发生毛细血管渗漏，而输注过量晶体液会加剧这种情况。当患儿的血流动力学稳定时(通常为24~48 h)，可使用超滤、连续性肾脏替代治疗(CRRT)和(或)利尿剂进行液体管理。利尿剂常以输注的方式给药，以避免抗凝不稳定。如果对利尿剂反应欠佳，则可使用缓慢持续超滤(SCUF)或CRRT清除液体。指南提出，对于出现的任何形式的肾衰竭，均可以考虑进行CRRT治疗。
2.5.4 镇静
总体目标是最小程度的镇静。新生儿最初的治疗通常是间断给药，但大多数情况下需持续输注。考虑到苯二氮䓬类药物对神经系统的不良影响，应尽量减少使用，可考虑使用右美托咪定作为镇静辅助药物。在插管、拔管和更换回路期间可考虑给予肌松药物以降低空气栓塞的风险。
2.5.5 营养管理
在ECMO治疗期间，新生儿可能会出现显著的分解代谢和体重下降，但一般不进行完全肠内营养，指南建议在可耐受的情况下缓慢增加喂养量。ECMO启动24 h内可开始肠外营养，热量目标为80~120 kcal/(kg.d)。部分中心为了避免液体超负荷而限制液体摄入量，因此，应该在限制液体的情况下尽量增加热量的摄入。此外，早期启动CRRT控制液体平衡已被证实可改善蛋白质的输送[13]。一些机构利用外周静脉导管输注脂肪乳剂，以避免脂肪沉积和血管内血栓形成。
2.5.6 温度
ECMO回路的血液温度应该与正常平均体温(通常为37 ℃)相匹配，可通过热交换器进行调节。为避免发生缺氧缺血性脑病(hypoxic ischemic encephalopathy，HIE)，并希望在最初的24~72 h维持轻度低温(33~34 ℃)，则可降低热交换器温度。现有证据表明，缺血损伤合并肝素化可能增加HIE患儿发生颅内出血的风险，而ECMO联合低温治疗则不会加重HIE[14]。然而，在需要关注HIE的情况下，如果在ECMO支持之前未给患儿降温，则在ECMO支持开始后再进行降温是没有益处的[15]，且可能掩盖感染或其他原因引起的发热。同时，该研究还指出，ECMO联合低温治疗可能影响患儿的远期认知水平[15]。因此，需要充分利用实验室检测指标(白细胞计数、血红蛋白浓度、酸中毒和血培养)结果来评估感染情况，以避免高代谢并识别潜在的感染。
2.5.7 感染和抗生素
目前，尚无关于ECMO支持期间是否应预防性使用抗生素或监测血培养的标准方案和支持数据，在新生儿ECMO中也未推荐预防性使用抗生素，因此，抗生素的使用应仅限于疑似或确诊感染的情况。ECMO期间的菌血症可能与回路某个部件上的细菌定植有关，但通常来源于患儿其他部位。如抗生素治疗期间血培养结果仍为阳性，则应考虑更换ECMO回路，但目前对于这一临床实践的数据有限。
2.5.8 外科手术
对于接受抗凝治疗的ECMO患儿，在进行外科手术时需特别关注出血问题。通常应考虑减少肝素输注量，并使血小板水平维持在(80~100 000)×109/L，纤维蛋白原>1.5 g/L时也可考虑抗纤溶疗法(如氨基己酸)。在有创操作前1 h和操作期间可停止抗凝，在再次出血风险降低后重新开始。如果在减少肝素用量和更换产品的情况下仍持续出现术后出血，则应停止抗凝直至出血停止，但这也可能导致回路血凝块形成。因此，对回路进行积极监测非常重要，尤其是对于流量相对较低的新生儿回路。
2.5.9 ECMO期间的影像学监测
头颅超声神经成像(neuroimaging head ultrasound，HUS)是新生儿神经影像学中的重要技术。常用的HUS方案包括在ECMO插管前获取基线超声影像，然后在插管后3~5 d(脑出血发生率最高的时间段)每天监测HUS，以及在ECMO运行期间以不同的时间间隔进行HUS检测[16-17]。当出现新的临床问题，如新发癫痫发作、血红蛋白突然下降等，也应进行HUS检测。
对于HUS异常患儿的随访和评估，目前使用头颅计算机断层扫描(CT)以评估可能影响患儿生存或继续ECMO运转的紧急情况。然而，头部CT对于灰质和白质损伤的检测并不敏感和特异。
磁共振成像(MRI)是检测颅内损伤和病变的金标准，尤其是卒中和白质损伤。但在ECMO运行时，无法进行MRI检查。增强MRI可在ECMO支持后或出院前进行。
2.5.10 脑电图(EEG)或振幅整合脑电图(aEEG)监测
危重症婴儿癫痫发生风险高，接受ECMO治疗的新生儿癫痫发生率为5%~30%，而其中大多数仅表现为脑电图异常[18-19]。神经内科医师通常会根据指南建议使用抗癫痫药物来治疗癫痫。
3 新生儿ECMO的并发症处理[5]
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3.1 ECMO回路空气
需立即进行处理，尤其是VA ECMO。常见的处理方案如下：(1)停止血泵并夹住动脉(输注)管路；(2)如果可能，通过侧支运转ECMO，将空气分流到回路的静脉部分；(3)检查回路是否有空气，并确定空气的来源；(4)清除回路中的空气，并查找漏气部位。
3.2 头部或脑实质出血
对于病情稳定的新生儿，在ECMO运行3~5 d，应每天进行一次HUS检测，之后按照各ECMO中心监测方案进行。如HUS检测显示出血，可通过CT扫描提供关于出血严重程度和进展的额外信息，并根据不同的出血程度，采取不同的诊疗方案：(1)对于小规模出血，需优化抗凝方案，并多次重复行HUS以检测出血是否扩大；(2)对于进行性出血或中度出血，应采取措施优化心肺支持，使患儿逐步脱离ECMO；(3)对于严重的脑实质内出血，可能需要撤除体外生命支持。
4 停用体外循环和拔管
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4.1 拔管
切开放置的套管，直接拔除插管，通常选择结扎血管，是否进行颈部血管重建由专业的外科医师和ECMO中心决定，但其效用尚未达成共识[20]。经皮放置的套管移除后通过按压该区域，并缝合此处皮肤进行止血，以促使这些血管长期通畅。
4.2 停止无效支持(不可逆)
如果疾病过程是不可逆的，应考虑停止使用ECMO，如发生严重的脑损伤或无法进行器官移植的器官衰竭。在患儿接受ECMO治疗前的知情同意过程中，应明确表示将多次重新评估是否继续使用ECMO。如果患儿在一段合理时间内未显示出任何改善，则可以考虑停止ECMO的使用。
5 总结与展望
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根据2023年4月ECLS报告，新生儿接受ECMO支持的存活率为45%~65%，其中患有肺疾病的新生儿在所有年龄段的ECMO患者中存活率最高。过去15年间，平均每次ECMO运行时间从约150 h增加至约200 h。较长的ECMO运行时间和较低的生存率表明，ECMO正越来越广泛地应用于并发症更多、病情更危重的患儿，因此优化ECMO支持技术尤为重要。该指南详细阐述了进行ECMO治疗的新生儿纳入标准、排除标准、模式选择及治疗期间的管理等方案，但未提供针对新生儿呼吸支持ECMO的最佳抗凝方案。鉴于该指南的不足，临床医师应结合患儿和医院的实际情况制定个性化的诊疗方案。同时，对于新生儿ECMO支持期间的抗凝治疗、体温管理、神经系统预后监测等仍需更高级别的证据以指导临床治疗，以进一步改善此类患儿的预后。
基金
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  • 国家重点研发计划(2021YFC2701700)
  • 首都卫生发展科研专项面上项目(2020-2-5093)
文献
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参考文献 引证文献
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Cuevas Guaman M, Lucke AM, Hagan JL, et al. Bleeding complications and mortality in neonates receiving therapeutic hypothermia and extracorporeal membrane oxygenation[J]. Am J Perinatol, 2018, 35(3): 271-276.
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Field D, Juszczak E, Linsell L, et al. Neonatal ECMO study of temperature (NEST): a randomized controlled trial[J]. Pediatrics, 2013, 132(5): e1247-e1256.
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2024年第49卷第3期
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文章信息
doi: 10.11855/j.issn.0577-7402.1016.2023.1228
  • 接收时间：2023-08-14
  • 首发时间：2025-11-23
  • 出版时间：2024-03-28
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  • 收稿日期：2023-08-14
  • 录用日期：2023-10-20
基金
National Key Research and Development Program of China(2021YFC2701700)
国家重点研发计划(2021YFC2701700)
Capital's Funds for Health Improvement and Research(2020-2-5093)
首都卫生发展科研专项面上项目(2020-2-5093)
作者信息
    1南方医科大学第二临床医学院，广东广州 510515
    2解放军总医院第七医学中心，北京 100700

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2种不同金属材料的力学参数
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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