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Article(id=1211268929662611757, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211268928383348982, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.02.16, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1585843200000, receivedDateStr=2020-04-03, revisedDate=1604937600000, revisedDateStr=2020-11-10, acceptedDate=null, acceptedDateStr=null, onlineDate=1766718617120, onlineDateStr=2025-12-26, pubDate=1614441600000, pubDateStr=2021-02-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766718617120, onlineIssueDateStr=2025-12-26, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766718617120, creator=13701087609, updateTime=1766718617120, updator=13701087609, issue=Issue{id=1211268928383348982, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='2', pageStart='107', pageEnd='211', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766718616815, creator=13701087609, updateTime=1766718805938, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1211269721685627740, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211268928383348982, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1211269721685627741, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211268928383348982, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=207, endPage=211, ext={EN=ArticleExt(id=1211268929977184576, articleId=1211268929662611757, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Research progress on safety and efficacy of intravascular cooling technique in the treatment of heat stroke, columnId=1190243275882729994, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Heat stroke is the most severe form of heat-related illness, characterized by an elevated core body temperature(> 40 ℃) and an altered level of central nervous system dysfunction. The primary goal of treatment for heat stroke is to lower core body temperature, and evidence suggests that timely cooling promotes survival with limited sequelae. Intravascular cooling technique is a new cooling technique gradually applied in intensive care medicine in recent years, which can directly cool or rewarm blood, and can provide a larger cooling rate than traditional cooling methods. The focus of this article is to review the research progress of intravascular cooling technique on clinical application, and discuss the feasibility and safety of intravascular temperature management for heat stroke.

, correspAuthors=Tan-Shi Li, authorNote=null, correspAuthorsNote=
*E-mail:
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热射病以核心体温升高(>40℃)及不同程度的中枢神经系统功能紊乱为特征，是热疾病中最严重的一种。快速有效地降低核心体温是临床治疗的首要措施，而冷却速率是决定热射病患者预后的关键因素之一。血管内降温技术是近年来逐渐应用于重症医学领域的一种新的降温技术，可直接对血液进行降温或复温，较传统降温方式能提供更高的冷却速率。该文就血管内降温技术的临床应用及其对热射病治疗的有效性和安全性进行综述。

, correspAuthors=黎檀实, authorNote=null, correspAuthorsNote=
黎檀实，E-mail：
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高建新，博士研究生，主治医师，主要从事急危重症疾病的临床研究。E-mail：

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高建新，博士研究生，主治医师，主要从事急危重症疾病的临床研究。E-mail：

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高建新，博士研究生，主治医师，主要从事急危重症疾病的临床研究。E-mail：

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血管内降温技术及其治疗热射病的有效性和安全性研究进展
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高建新 , 黎檀实 *
解放军医学杂志 | 综述 2021,46(2): 207-211
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解放军医学杂志 | 综述 2021, 46(2): 207-211
血管内降温技术及其治疗热射病的有效性和安全性研究进展
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高建新, 黎檀实*
作者信息
  • 解放军总医院第一医学中心急诊科，北京 100853

    • 高建新，博士研究生，主治医师，主要从事急危重症疾病的临床研究。E-mail：

通讯作者:

黎檀实，E-mail：
Research progress on safety and efficacy of intravascular cooling technique in the treatment of heat stroke
Jian-Xin Gao, Tan-Shi Li*
Affiliations
  • Department of Emergency, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
出版时间: 2021-02-28 doi: 10.11855/j.issn.0577-7402.2021.02.16
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摘要
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热射病以核心体温升高(>40℃)及不同程度的中枢神经系统功能紊乱为特征，是热疾病中最严重的一种。快速有效地降低核心体温是临床治疗的首要措施，而冷却速率是决定热射病患者预后的关键因素之一。血管内降温技术是近年来逐渐应用于重症医学领域的一种新的降温技术，可直接对血液进行降温或复温，较传统降温方式能提供更高的冷却速率。该文就血管内降温技术的临床应用及其对热射病治疗的有效性和安全性进行综述。

热射病  /  血管内降温  /  治疗措施

Heat stroke is the most severe form of heat-related illness, characterized by an elevated core body temperature(> 40 ℃) and an altered level of central nervous system dysfunction. The primary goal of treatment for heat stroke is to lower core body temperature, and evidence suggests that timely cooling promotes survival with limited sequelae. Intravascular cooling technique is a new cooling technique gradually applied in intensive care medicine in recent years, which can directly cool or rewarm blood, and can provide a larger cooling rate than traditional cooling methods. The focus of this article is to review the research progress of intravascular cooling technique on clinical application, and discuss the feasibility and safety of intravascular temperature management for heat stroke.

heat stroke  /  intravascular cooling  /  treatment measures
高建新, 黎檀实. 血管内降温技术及其治疗热射病的有效性和安全性研究进展. 解放军医学杂志, 2021 , 46 (2) : 207 -211 . DOI: 10.11855/j.issn.0577-7402.2021.02.16
Jian-Xin Gao, Tan-Shi Li. Research progress on safety and efficacy of intravascular cooling technique in the treatment of heat stroke[J]. Medical Journal of Chinese People’s Liberation Army, 2021 , 46 (2) : 207 -211 . DOI: 10.11855/j.issn.0577-7402.2021.02.16
正文
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热射病(heat stroke，HS)是指由于暴露在高温环境下，导致体温调节功能障碍，核心体温升高(>40 ℃)，以至出现谵妄、抽搐、昏迷等中枢神经系统功能障碍表现，并伴有多器官不同程度损伤的疾病[1-2]。根据热暴露过程中是否存在劳累因素分为经典型热射病(classical heat stroke，CHS)和劳力性热射病(exertional heat stroke，EHS)。如不给予迅速有效的治疗，热射病可造成永久性脑损害，肝、肾衰竭及凝血功能障碍，甚至死亡[3]。热射病的核心治疗方案是快速有效地降温和器官功能支持。关于热射病降温方式的选择，目前仍缺少大型临床研究证据支持，且尚无统一标准[4]。血管内降温技术的特点是降温迅速可靠，热交换效率较体表降温方式高，创伤较体外循环降温小，在院外心跳骤停、急性心肌梗死和急性脑卒中等患者的治疗中应用广泛[5-7]。血管内降温技术是一种安全、有效、可行的降温技术，近年来被越来越多的研究者应用于热射病患者的体温管理。本文对血管内降温技术的临床应用及其治疗热射病的有效性和安全性进行综述。
1 血管内降温技术的临床应用进展
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广义的血管内降温技术包括血管内灌注降温，即静脉快速输注大量冷却液体以达到降温的目的，但会影响对患者的液体管理，且不易准确调节体温，其临床应用受到限制。本文探讨的血管内降温技术特指血管内热交换降温技术，即采用介入方法将温度控制导管置入人体的深静脉，通过体外机使冷却液在热交换器和导管之间循环，从而直接对血液进行降温。
1.1 血管内降温系统
血管内降温相关产品主要有Celsius控制系统(美国Innercool Therapies公司)、Reprieve系统(美国Radiant Medical公司)及CoolGard系统(美国ZOLL医疗公司)等，3种降温系统的工作原理相似，都具有持续体温监测和自动温度控制功能，主要不同点为降温导管的设计。Celsius控制系统工作时，主机将约150 ml无菌生理盐水进行冷却，泵入导管完成闭环循环，导管远端装有一个柔性金属传热元件，可直接与周围血液进行热交换[8]。Reprieve系统工作方式与之类似，主要不同点是降温导管的远端为波纹状软管，冷却液在波纹管中循环并与周围血液进行热交换[9]。CoolGard系统的降温导管有多种不同规格，如Quattro、Icy和Cool Line导管远端设有2~3个同轴的球囊结构，而Solex 7导管远端为蛇形排列的球囊，系统将冷却液泵入球囊形成特有的涡流，从而与周围血液进行热交换。上述3种降温系统所使用的导管表面都包被有肝素，以抑制管周血栓的形成。
Celsius控制系统和Reprieve系统所使用的导管需经股静脉置入，CoolGard系统的Solex 7需经锁骨下静脉或颈内静脉置入，Quattro和Icy需经股静脉置入，而Cool Line适用于上述3种穿刺途径。不同产品的理论最大降温或复温功率不同，导管相关感染、深静脉血栓、心律失常、动脉损伤和气胸等并发症的发生可能与导管管径、穿刺部位、置入深度和留置时间等因素相关[10-11]，但目前尚无研究比较上述产品在临床应用中的有效性和安全性。Celsius控制系统在动物实验[8]和临床试验[12]中被证实可有效降低机体核心体温，且不良反应很少，但InnerCool的体温管理业务已被ZOLL公司收购，近年来很少有文献报道Celsius控制系统的临床使用情况。Reprieve系统已上市多年且在部分临床试验中证实了其降温的有效性，但关于这一降温系统的文献报道十分有限，可能与其尺寸较大，不利于长时间的体温控制等原因有关[13]。目前CoolGard系统在血管内降温领域应用最为广泛[14-19]。
1.2 血管内降温技术在亚低温治疗中的应用
亚低温治疗是一种重要的体温管理手段，可保护重要脏器，改善中枢神经系统功能，被广泛用于心跳骤停复苏后治疗、心脏及神经外科手术、颅脑损伤及脑卒中的治疗等领域[20]，其作用机制包括降低代谢需求，维持机体能量平衡，减轻氧化应激损伤和再灌注损伤等[21]。诱导体温下降的方式包括体表降温、静脉输注冰盐水、药物降温及血管内降温等。
与其他降温手段相比，血管内降温技术在亚低温治疗的临床应用中表现出快速、平稳和便于控制的优点。Hoedemaekers等[22]开展的一项对比重症监护室常用亚低温治疗方法的研究发现，在冷却速率方面，血管内降温[(1.46±0.42) ℃/h]明显优于传统降温方式[(0.31±0.23) ℃/h，如静脉输注冰盐水、冰块冷敷等]和空气循环降温毯[(0.18±0.2) ℃/h]，且在维持低温状态方面更加可靠。De Fazio等[23]的研究发现，与体表降温方式相比，血管内降温可更加精确地降低院外心跳骤停患者的体温。两项Meta分析结果显示，与体表降温方式相比，使用血管内降温技术对院外心跳骤停患者实施亚低温治疗虽不能降低病死率，但可显著改善患者的神经系统功能预后[6,24]。
有研究发现，亚低温治疗可改善热射病患者的全身情况和预后[25-26]，这些研究中诱导亚低温的方式多为冰毯机等无创降温方式。从理论上讲，通过血管内降温技术诱导亚低温状态也可用于热射病的治疗，且能较传统方法更快速、稳定地控制体温，但目前为止国内外均无相关文献报道，其有效性和安全性有待进一步研究。
1.3 血管内降温技术用于过热患者的降温治疗
发热是由于下丘脑体温调定点上调而引起的调节性体温升高，通常继发于感染等全身炎症反应，物理降温和退热剂在多数发热患者中可有效降温，一般不需侵入性降温方式[27]。过热属非调节性体温升高，是由于体温调节障碍(如下丘脑损伤)、散热障碍(如中暑)或产热器官功能异常(如甲亢)等引起的体温升高，可迅速发展为多器官衰竭(multiple organ failure，MOF)甚至死亡，一旦诊断应积极开始降温治疗。
脑出血、脑外伤和脑卒中等患者如出现过热，普通降温方式通常效果有限[28]，而血管内降温技术可作为有效的体温管理方式。一项纳入蛛网膜下腔出血、脑出血、缺血性脑梗死和脑外伤患者的研究，将血管内降温技术应用于体温升高患者的降温治疗，结果显示，与药物+物理降温相比，血管内降温可更有效地减少患者的体温曲线下面积[28]。一项纳入102例脑血管疾病患者的随机对照研究发现，血管内降温较药物+物理降温更有效地降低了患者的体温[29]。
抗精神病药物致恶性综合征引起的过热，因体温调节中枢的调定点并未发生改变，退热剂一般无效[30]。降温治疗一般以物理方法为主，但通常效果有限，即使辅以药物治疗，也可能无法降至目标体温。Diedler等[31]首次使用血管内降温方式治疗1例诊断为抗精神病药物致恶性综合征的患者，其体温迅速得到控制，状态明显改善，血清肌酸激酶也有所下降。Mathieu等[32]报道的病例中，血管内降温也有效降低了抗精神病药物致恶性综合征患者的体温。
2 血管内降温技术治疗热射病的有效性
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热射病引起的体温升高属于过热，多项研究证实血管内降温技术可用于热射病的降温。迅速降温对于热射病的治疗至关重要，可减轻并发症和改善预后。临床使用的降温方法主要包括通过热传导、蒸发、对流等方式进行物理降温，例如通过连续肾替代治疗(CRRT)、冰盐水灌胃或灌肠等侵入性体内降温，以及药物降温等。目前，全身冷水浸浴降温法被认为是对热射病患者最为有效的降温方式[4]，但对于老年患者和合并心脏基础疾病的患者安全性较差[14]。此外，由于受空间和设备等的限制，冷水浸浴降温法在医院急诊部门的实施非常困难[19]。CRRT有利于降低热射病患者的炎性因子水平，减轻器官损害，降低病死率，而且治疗期间可控制置换液的温度及流速，使大量低温置换液与血液进行交换，从而快速有效地降低患者体温[33]。但CRRT没有负反馈的自动温度调控系统，治疗过程中需人工更换不同温度的置换液，可能会出现体温过低或者波动过大等情况。2004年Mégarbane等[17]的病例报告首次证实了血管内降温技术应用于热射病的有效性：当积极的物理降温对1例重症热射病患者体温控制欠佳时，研究者为患者经股静脉放置降温导管并启动血管内降温，在最大冷却速率(0.7 ℃/h)下3.5h即达到目标体温，5 d后停止血管内降温，最终该患者预后良好。Broessner等[18]的病例报告中，1例初始体温为40.8 ℃的热射病患者在最初20 h内接受了大剂量的非甾体类抗炎药及阿片类药物，并且联合应用了控温毯，但患者的核心体温仍未明显下降，此时研究者启动血管内降温，在最大冷却速率(0.6 ℃/h)下7 h即达到目标体温，后续5 d体温维持在(37.5±0.2) ℃，最终该患者预后良好，未遗留神经功能缺陷，表明在热射病患者体温控制困难时，血管内降温技术可作为有效的替代降温措施。
为了进一步证实血管内降温技术应用于热射病治疗的有效性，Yokobori等[14]开展了一项前瞻性多中心研究，纳入10个急诊医学中心收治的重症热射病患者，最终所有应用血管内降温技术治疗的患者均在最初24 h内达到理想体温，而传统降温组仅有50%达到理想体温；此外，血管内降温组在最初24 h内序贯器官衰竭评分(SOFA)明显下降，而传统降温组并未观察到这一变化。
血管内降温技术应用于热射病患者体温管理的文献报道目前仍较少，笔者共检索到5篇病例报告[15-19]和1篇多中心研究[14]，国内暂无相关文献。虽然这些研究中使用血管内降温的病例都得到了有效的体温控制，但文献的证据等级比较低，仅有的1篇多中心研究也有明显的局限性：样本量较小且未采取随机化方式分组。因此仍须开展大型临床研究进一步评估血管内降温技术应用于热射病体温管理的有效性。
3 血管内降温技术治疗热射病的安全性
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血管内降温技术属于有创操作，在评估其安全性时，需要首先考虑导管相关出血、感染和静脉血栓等不良反应。Hamaya等[15]在病例报告中提出应用血管内降温的热射病患者无导管相关出血、感染和血栓等并发症发生，而另外4篇病例报告未提及相关并发症的发生情况[16-19]。Yokobori等[14]开展的多中心研究中，血管内降温组患者均未发生深静脉血栓和肺栓塞，研究者认为这一结果可能与导管留置时间较短(24 h)和热射病相关凝血功能异常有关。
部分研究提出血管内降温导管可能增加静脉血栓形成的风险[34-35]，但目前并无高质量的研究证实血管内降温导管比普通中心静脉导管更容易导致血行感染或血栓形成。而多数重症热射病患者治疗早期需要留置中心静脉导管以便于液体复苏，因此笔者认为导管相关并发症目前不应作为限制血管降温技术用于热射病治疗的障碍，但在应用过程中仍应警惕这些并发症，尽量缩短导管留置时间并采取必要的抗血栓方案。
对于热射病患者，体温过高带来的危害大于过度降温，但仍应尽量避免过度低体温的发生[36]。血管内降温技术具有负反馈的温度调节功能，可最大程度地降低过度降温的风险。针对院外心跳骤停患者的研究发现，血管内降温引起体温过低的风险低于体表降温方式[6]。寒战是机体对抗降温治疗的常见不良反应，可引起呼吸、心率加快，耗氧量增加，血压和颅内压升高等，因此应积极主动地预防和处理寒战[13]。亚低温相关研究发现，与体表降温方式相比，血管内降温不会增加或降低寒战等的发生风险[6,37]，但可使消除寒战的过程更为简单。目前已有研究发现，采用静滴哌替啶、口服丁螺环酮和皮肤保温的方法能明显减轻患者的寒战反应[5]。血管内降温技术应用于热射病的降温治疗时，无需像亚低温治疗一样将预设温度降至35 ℃以下，当预设温度与反馈温度相差较小时，引起寒战的风险也更小[22]。关于血管内降温技术治疗热射病的文献并未报道寒战的发生情况，但实际应用中仍需警惕寒战的发生。
热射病的病理生理机制非常复杂，在考虑血管内降温技术的安全性时，同时需考虑潜在的心、肺、肝、肾、脑功能以及凝血功能不全加重的风险。Yokobori等[14]的研究采用常见不良反应事件评价标准(common terminology criteria for adverse events，CTCAE)，根据严重不良事件发生情况评估血管内降温技术的安全性，结果发现，实验组与对照组的不良事件发生率相似(P=0.17)，表明血管内降温不会增加热射病患者发生严重不良事件的风险。
4 总结与展望
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部分病例报告和小样本研究初步证实了血管内降温技术用于热射病降温治疗的有效性和安全性，但仍须开展大型的随机对照研究进一步评估其临床获益及风险。在热射病的临床治疗中，应根据患者的病情程度、基础疾病、经济条件，以及医院可提供的医疗设备等多方面综合考虑，选择最合适的降温方式，具备条件时可启动血管内降温治疗方案，但治疗过程中必须警惕导管相关并发症的发生。
基金
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  • 解放军总医院临床科研扶持基金(2018FCWJFWZX-2-11)
文献
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参考文献 引证文献
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2021年第46卷第2期
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doi: 10.11855/j.issn.0577-7402.2021.02.16
  • 接收时间：2020-04-03
  • 首发时间：2025-12-26
  • 出版时间：2021-02-28
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  • 收稿日期：2020-04-03
  • 修回日期：2020-11-10
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Clinical Research Support Fund of Chinese PLA General Hospital(2018FCWJFWZX-2-11)
解放军总医院临床科研扶持基金(2018FCWJFWZX-2-11)
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    解放军总医院第一医学中心急诊科，北京 100853

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