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Article(id=1241311710569623779, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241311708883513558, articleNumber=null, orderNo=null, doi=10.14109/j.cnki.xyylc.2024.01.03, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1653321600000, receivedDateStr=2022-05-24, revisedDate=null, revisedDateStr=null, acceptedDate=1692547200000, acceptedDateStr=2023-08-21, onlineDate=1773881374255, onlineDateStr=2026-03-19, pubDate=1706112000000, pubDateStr=2024-01-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773881374255, onlineIssueDateStr=2026-03-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773881374255, creator=13701087609, updateTime=1773881374255, updator=13701087609, issue=Issue{id=1241311708883513558, tenantId=1146029695717560320, journalId=1205117082300743687, year='2024', volume='43', issue='1', pageStart='1', pageEnd='78', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773881373854, creator=13701087609, updateTime=1773882024061, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241314436116435425, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241311708883513558, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241314436116435426, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241311708883513558, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=12, endPage=16, ext={EN=ArticleExt(id=1241311710896779496, articleId=1241311710569623779, tenantId=1146029695717560320, journalId=1205117082300743687, language=EN, title=Progress of esketamine application in perioperative period, columnId=1207314219599499390, journalTitle=Chinese Journal of New Drugs and Clinical Remedies, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Esketamine is a powerful narcotic analgesic, which has been used in clinical anesthesia and postoperative analgesia. Esketamine can be administered through a variety of ways, with strong analgesic effect, rapid onset, rapid elimination, and no inhibition of spontaneous respiration. It has certain advantages in pediatric anesthesia, obstetric anesthesia, and anesthesia in patients with low blood volume or burn, and is suitable for elderly patients. So esketamine is widely used in clinic. However, the dosage, application method and the choice of combination drugs of esketamine remain to be further discussed.

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艾司氯胺酮是一种强效麻醉性镇痛药，目前已用于临床麻醉和术后镇痛中。艾司氯胺酮可通过多种途径给药，有镇痛作用强、起效迅速、消除迅速、不抑制自主呼吸的优点，在小儿麻醉、产科麻醉以及低血容量患者或烧伤患者的麻醉中有一定的优势，且适用于老年患者，在临床中的应用日益广泛。但艾司氯胺酮的使用剂量、应用方法及联用药物的选择等尚有待进一步探讨。

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苏帆，E-mail：
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王群，女，副主任医师，博士在读，主要从事临床麻醉的研究，E-mail：

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王群，女，副主任医师，博士在读，主要从事临床麻醉的研究，E-mail：

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王群，女，副主任医师，博士在读，主要从事临床麻醉的研究，E-mail：

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艾司氯胺酮在围手术期的应用进展
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王群 1, 2 , 季加富 2 , 迟永良 2 , 苏帆 2
中国新药与临床杂志 | 综述 2024,43(1): 12-16
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中国新药与临床杂志 | 综述 2024, 43(1): 12-16
艾司氯胺酮在围手术期的应用进展
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王群1, 2 , 季加富2, 迟永良2, 苏帆2
作者信息
  • 1.山东中医药大学第一临床医学院，山东 济南　250014
  • 2.山东中医药大学附属医院 麻醉科，山东 济南　250014

    • 王群，女，副主任医师，博士在读，主要从事临床麻醉的研究，E-mail：

通讯作者:

苏帆，E-mail：
Progress of esketamine application in perioperative period
Qun WANG1, 2 , Jia-fu JI2, Yong-liang CHI2, Fan SU2
Affiliations
  • 1.The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Ji-nan SHANDONG 250014, China
  • 2.Department of Anesthesiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji-nan SHANDONG 250014, China
出版时间: 2024-01-25 doi: 10.14109/j.cnki.xyylc.2024.01.03
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摘要
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艾司氯胺酮是一种强效麻醉性镇痛药，目前已用于临床麻醉和术后镇痛中。艾司氯胺酮可通过多种途径给药，有镇痛作用强、起效迅速、消除迅速、不抑制自主呼吸的优点，在小儿麻醉、产科麻醉以及低血容量患者或烧伤患者的麻醉中有一定的优势，且适用于老年患者，在临床中的应用日益广泛。但艾司氯胺酮的使用剂量、应用方法及联用药物的选择等尚有待进一步探讨。

艾司氯胺酮  /  麻醉  /  镇痛  /  围手术期  /  镇静

Esketamine is a powerful narcotic analgesic, which has been used in clinical anesthesia and postoperative analgesia. Esketamine can be administered through a variety of ways, with strong analgesic effect, rapid onset, rapid elimination, and no inhibition of spontaneous respiration. It has certain advantages in pediatric anesthesia, obstetric anesthesia, and anesthesia in patients with low blood volume or burn, and is suitable for elderly patients. So esketamine is widely used in clinic. However, the dosage, application method and the choice of combination drugs of esketamine remain to be further discussed.

esketamine  /  anesthesia  /  analgesia  /  perioperative period  /  sedation
王群, 季加富, 迟永良, 苏帆. 艾司氯胺酮在围手术期的应用进展. 中国新药与临床杂志, 2024 , 43 (1) : 12 -16 . DOI: 10.14109/j.cnki.xyylc.2024.01.03
Qun WANG, Jia-fu JI, Yong-liang CHI, Fan SU. Progress of esketamine application in perioperative period[J]. Chinese Journal of New Drugs and Clinical Remedies, 2024 , 43 (1) : 12 -16 . DOI: 10.14109/j.cnki.xyylc.2024.01.03
正文
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艾司氯胺酮是氯胺酮的右旋异构体，主要通过阻滞N-甲基-D-天冬氨酸（NMDA）受体来发挥镇痛作用，与氯胺酮相比具有镇痛作用更强、体内消除更快且更可控、精神类不良反应更少、神经保护作用更显著等优点[1,2]，且可以通过多种途径给药。艾司氯胺酮在临床中的应用越来越广泛，并取得了较满意的效果，故此笔者综述艾司氯胺酮在围手术期的应用进展，以期为其的临床合理应用提供参考。
给药途径
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艾司氯胺酮的给药途径较多，有静脉注射（静注）、肌内注射、雾化吸入、口服、直肠和鼻黏膜给药等。静脉给药是临床常用的方式，艾司氯胺酮单次给药0.125 ~ 0.25 mg·kg-1即可发挥镇静、镇痛作用，对于时间较长的手术可采用持续静脉输注以维持患者适当的镇静和镇痛状态[3]。对于静脉通路建立困难或不合作的患者，肌内注射也是常用的给药方式，尤其适用于小儿麻醉诱导；艾司氯胺酮还可雾化吸入，药物在呼吸道局部沉积而发挥扩张气管的作用，适用于支气管哮喘患者[4]。对于无法肌内或静脉给药的患者，还可以采用直肠给药，直肠给药的生物利用度为30%；鼻内给药简单方便，也是目前常用的给药方式，值得注意的是此途径药物生物利用度高达45%，给药剂量需要加以精准调控[5]。目前，艾司氯胺酮的椎管内给药及关节腔给药的具体方案仍待探索。
艾司氯胺酮在围手术期的应用
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1　在小儿麻醉中的应用
大多数患儿在手术前有明显的焦虑，这会影响吸入麻醉诱导的效果，甚至出现诱导困难，而强行诱导又可能会导致患儿的心理创伤，从而使术后躁动的发生率增加，甚至会导致患儿术后不良行为的发生，且对术后镇痛的需求增加[6]。因此，平稳的麻醉诱导显得尤为重要，艾司氯胺酮可经鼻给药的优点在此方面得到发挥。LU等[7]将90例1 ~ 6岁患儿均分为3组，吸入麻醉诱导前分别经鼻给予右美托咪定2 µg·kg-1（D组）、艾司氯胺酮1 mg·kg-1（S组）、右美托咪定1 µg·kg-1联合艾司氯胺酮0.5 mg·kg-1（DS组），结果显示，DS组患儿的诱导配合满意度评分（ICC评分）明显低于D组和S组（ICC评分越低表示配合满意度越好），镇静成功率达90%，高于D组（70%）和S组（53.3%），而术后躁动和谵妄的发生率显著低于D组和S组，提示术前经鼻给予艾司氯胺酮0.5 mg·kg-1联合右美托咪定1 µg·kg-1可提高患儿麻醉诱导的成功率，并减少术后躁动等不良反应的发生。艾司氯胺酮联合右美托咪定也适用于某些特殊疾病患儿，如先天性心脏病患儿心功能比较差，良好的术前镇静不仅可有效缓解焦虑，更有利于减轻心脏负担，从而提高围术期的安全性。曹泷尹等[8]在先天性心脏病患儿术前给予右美托咪定复合艾司氯胺酮滴鼻，发现镇静起效时间明显短于右美托咪定单用，且患儿心率更平稳。也有研究显示，小儿全身麻醉（全麻）前静脉给予小剂量艾司氯胺酮（0.3 mg·kg-1）能降低苏醒期躁动的发生率[9]。在儿科急诊中艾司氯胺酮已逐步替代阿片类药物，PATEL等[10]回顾性分析了行手法复位术的151例前臂骨折急诊患儿的资料，发现应用艾司氯胺酮后患儿均顺利完成手术，随访显示89.1%的患儿复位成功，无需切开治疗，证实了艾司氯胺酮在急诊骨折患儿手法复位术中应用的安全性和有效性。WANG等[11]将120例下肢骨折患儿随机均分为2组，分别采取超声引导下的神经阻滞联合艾司氯胺酮0.5 mg·kg-1和超声引导下的神经阻滞联合全麻，结果显示2组麻醉效果无显著差异，但神经阻滞联合艾司氯胺酮组患儿术后恶心呕吐、血管损伤的发生率显著低于神经阻滞联合全麻组（P < 0.05），说明在区域阻滞麻醉中，艾司氯胺酮不仅能起到良好的辅助镇痛作用，其交感神经兴奋作用可以使患儿血管充盈性较联合全麻更好，超声下显示更清晰，从而降低神经阻滞时血管损伤的发生率。在普外科急诊中，van de BUNT等[12]观察到肠套叠患儿水压灌肠复位时，应用艾司氯胺酮静脉镇静的患儿比应用吗啡的患儿复位成功率更高（90% vs.70%），且肠套叠的复发率更低，从而手术时间和住院时间缩短。此外，小儿应用艾司氯胺酮后发生的不良反应如分泌物过多、头晕、眼球震颤等非常罕见，喉痉挛的发生率估计在0.017%以下，与成人相比，精神类不良反应的发生率也显著降低[13,14]。
2　在特殊情况和特殊人群中的应用
艾司氯胺酮有交感神经兴奋作用，给药后可使血压回升、心率增快，因此适用于老年或休克患者的麻醉诱导，以减轻丙泊酚和阿片类药物诱导时出现的心血管系统抑制，使血流动力学更加平稳。TU等[15]将80例年龄60岁以上的全麻手术老年患者随机分为2组，每组40例，对照组麻醉诱导给予丙泊酚4 µg·L-l复合舒芬太尼0.4 µg·kg-1靶控输注，研究组给予丙泊酚4 µg·L-l靶控输注复合艾司氯胺酮0.5 mg·kg-l单次注射，2组均采用丙泊酚4 mg·kg-l维持麻醉。结果显示，研究组诱导后和手术结束时血肾上腺素、去甲肾上腺素和内皮素浓度显著低于对照组（P < 0.05），术后24 h患者蒙特利尔认知评分显著高于对照组（P < 0.05），意识恢复时间显著短于对照组（P < 0.05），说明艾司氯胺酮复合丙泊酚有可能改善老年患者全麻期间的血流动力学，减轻手术应激和炎症反应，术后苏醒更快。也有研究者将不同剂量艾司氯胺酮用于老年患者全麻诱导，将120例65 ~ 80岁患者分为4组，每组30例，分别给予艾司氯胺酮0.3、0.4、0.5 mg·kg-1和舒芬太尼0.5 µg·kg-1复合丙泊酚进行麻醉诱导，结果显示艾司氯胺酮0.4 mg·kg-1复合丙泊酚组患者全麻诱导期间血流动力学最为稳定且术后谵妄的发生率较低[16]，也证实了艾司氯胺酮可以替代舒芬太尼用于老年患者的麻醉诱导。
临床常用剂量的艾司氯胺酮对自主呼吸影响较小，并可以保持气道通畅、降低气道阻力，这对于严重烧伤瘢痕导致的张口困难、颏胸黏连，无法对气道进行操作的患者具有独特优势，因此还常用于烧伤患者反复换药和皮瓣移植手术的麻醉[17]。另外，艾司氯胺酮也是为数不多可单独应用于紧急剖腹产手术麻醉的药物之一[18]。艾司氯胺酮还具有扩张支气管、松弛气道的作用，可有效缓解支气管痉挛、改善通气和换气功能，因此可用于哮喘患者的治疗或麻醉[4]。
3　在门诊或短小手术中的应用
由于艾司氯胺酮作用时间短、镇痛和镇静作用较强，其也适用于无痛胃肠镜检查或门诊短小手术的麻醉。WANG等[19]进行了一项随机、开放、平行对照试验，将32例行无痛胃镜检查患者随机均分成2组，分别给予艾司氯胺酮0.5 mg·kg-1单次静注复合丙泊酚和氯胺酮1 mg·kg-1单次静注复合丙泊酚，发现与氯胺酮组相比，艾司氯胺酮组患者的意识恢复时间更短（13 min vs.9 min），方向感恢复时间也更短（17 min vs. 11.5 min），不良反应（头晕、恶心、呕吐、头痛、疲劳等）发生率更低（87.5% vs. 75%），说明艾司氯胺酮0.5 mg·kg-1静注复合丙泊酚用于无痛胃镜检查安全有效，患者耐受性好。此外，有研究发现在无痛胃肠镜检查中，艾司氯胺酮0.25 mg·kg-1静注复合丙泊酚较丙泊酚单用麻醉起效时间更短（14 s vs. 27 s），丙泊酚的追加用量更小（71 mg vs. 111 mg），患者血流动力学更稳定，且呼吸抑制、呛咳、体动等不良反应的发生率显著降低（P < 0.05）[20]。张忠其等[21]研究证实，艾司氯胺酮复合丙泊酚抑制胃镜置入反应的半数有效剂量及95%有效剂量分别为1.691 mg· kg-1和2.032 mg·kg-1。内镜逆行性胰胆管造影（ERCP）是一种复杂的内镜诊疗方法，操作时间长、多伴疼痛，且患者需长时间保持固定体位，因此需在深度镇静或全麻下进行。EBERL等[22]将166例行ERCP的患者分为2组，分别给予艾司氯胺酮150 µg·kg-1（E组）或阿芬太尼2 µg·kg-1（A组）诱导，以改良警觉/镇静量表（MOAA/S）评分设置丙泊酚的靶浓度，如MOAA/S评分高于2分但患者仍有体动不能耐受手术时，每3 min增加丙泊酚血浆靶浓度0.5 µg·mL-1，同时相应地加入艾司氯胺酮50 µg·kg-1或阿芬太尼1 µg·kg-1。E组完成83例，A组完成79例，E组丙泊酚总用量显著少于A组（8.3 mg·kg-1·h-1 vs. 10.5 mg·kg-1·h-1，P < 0.001），且镇静效果令人满意，2组患者意识恢复时间、患者和内镜医师满意度无显著差异，提示艾司氯胺酮和阿芬太尼复合丙泊酚都可以安全地用于ERCP术的麻醉，且艾司氯胺酮复合丙泊酚可减少丙泊酚的应用量。儿童在门诊检查中常不能合作，多单纯应用丙泊酚镇静，虽然高效、迅速，但存在呼吸抑制、气道保护性反射消失等缺点，刘玉静等[23]将艾司氯胺酮0.5 mg·kg-1复合丙泊酚1.5 mg·kg-1应用于行MRI检查的患儿，与丙泊酚单用组相比，复合组丙泊酚总量、气道相关的不良事件及低血压、心动过缓的发生率显著降低（P < 0.05），提示艾司氯胺酮复合丙泊酚优于单独使用丙泊酚。
4　在术后镇痛中的应用
小剂量艾司氯胺酮即有镇痛作用，其作用机制可能为以下几个方面[24,25]：（1）拮抗NMDA受体，选择性阻断脊髓网状结构对痛觉信号的传入，从而阻断疼痛的传导；（2）拮抗NMDA受体，抑制中枢敏化，降低阿片耐受和痛觉过敏，从而提高镇痛效果；（3）作用于阿片δ受体，改善µ受体功能。从理论上讲，艾司氯胺酮可安全地应用于术后镇痛。丰浩荣等[26]研究发现，在阴茎矫正术术后镇痛中，与单纯应用芬太尼20 µg·kg-1自控静脉镇痛相比，应用艾司氯胺酮0.72 mg·kg-1复合芬太尼20 µg·kg-1自控静脉镇痛患儿术后补救镇痛率及术后12、24 h的血糖、C反应蛋白浓度显著降低（P < 0.05）。同样，食管癌根治术术后镇痛中，与单纯应用舒芬太尼自控静脉镇痛相比，应用艾司氯胺酮0.03 mg·kg-1复合舒芬太尼2 µg·kg-1自控静脉镇痛的患者术后4、8、24、48 h的疼痛视觉模拟量表（VAS）评分更低，48 h内按压镇痛泵的次数更少，并且术后48 h血白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α的水平显著降低（P < 0.05）[27]。更有研究发现，术中持续输注艾司氯胺酮可以在术后很长一段时间内发挥镇痛作用。LEI等[28]进行了一项多中心、随机、双盲对照临床试验，将914例接受胸腔镜手术的患者按1∶1分成2组。艾司氯胺酮组全麻诱导后静脉给予艾司氯胺酮0.1 mg·kg-1，术中持续输注0.1 mg·kg-1·h-1，术后48 h内自控静脉镇痛给予艾司氯胺酮0.015 mg·kg-1·h-1复合舒芬太尼0.03 µg·kg-1·h-1，而对照组诱导和维持均静脉给予氯化钠注射液，术后自控静脉镇痛单纯给予舒芬太尼0.03 µg·kg-1·h-1，术后3个月内艾司氯胺酮组VAS评分低于对照组，提示术中及术后应用艾司氯胺酮在胸腔镜术后仍能提供较长时间良好的镇痛作用。WANG等[29]对艾司氯胺酮静注治疗成人术后急性疼痛进行了系统综述和荟萃分析，认为围手术期应用艾司氯胺酮能够有效地辅助镇痛，可降低术后短时间内疼痛的强度和对阿片类药物的需求。但ITHNIN等[30]在妇科开腹手术的患者中进行了一项试验，分别在切皮前和切除子宫后静脉给予艾司氯胺酮0.25 mg·kg-1，结果显示术后吗啡的总用量未减少，因此研究者认为艾司氯胺酮的镇痛作用较小，考虑与艾司氯胺酮给药剂量和给药时机不当有关。
安全性
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与氯胺酮相似，麻醉剂量的艾司氯胺酮也可以使患者产生分离麻醉的状态，偶尔会触发产生不愉快的梦境，甚至是明显的幻觉，这些不良反应通常可以通过与丙泊酚或咪达唑仑联用而被完全抑制。CHU等[31]发现单次小剂量右美托咪定（0.25 µg·kg-1）可有效减轻艾司氯胺酮诱导的小鼠拟精神病性不良反应，且不影响麻醉恢复时间，可能是因为右美托咪定可以抑制艾司氯胺酮诱导的脑内c-Fos的表达。艾司氯胺酮还具有阻滞胆碱M受体的作用，进而增加支气管黏液的分泌，这一点可以使用阿托品来拮抗[3]，并注意及时吸引避免误吸。另外，艾司氯胺酮常见的不良反应包括恶心、呕吐、视力下降、头晕等，这些不良反应可以通过5-羟色胺受体拮抗剂来抑制，其机制尚不清楚，可能与两者对受体的相互作用有关。
综上所述，目前艾司氯胺酮在围手术期的应用范围主要集中在麻醉诱导、维持以及辅助镇痛方面，尤其是在产科凶险状况的快速麻醉、低血容量及休克患者的诱导、伴有哮喘性疾病患者的麻醉以及镇痛不全补偿麻醉方面有相对较大的应用优势，越来越受到麻醉医生的青睐。针对艾司氯胺酮的药物精准配伍方面的研究尚不够深入，如何降低其心肌负性作用，克服其心血管兴奋作用、分离麻醉状态、麻醉后不良情绪反应及用药个体差异等将是今后的重要研究方向。配伍应用的丙泊酚有心血管抑制作用、快速镇静以及愉快的情绪反应，与艾司氯胺酮药理作用有一定协同和拮抗效应，但有待前瞻性、大样本、多中心的随机对照研究进一步明确。
基金
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  • 济南市科技创新发展计划(202134068)
  • 山东省自然科学基金面上项目(ZR2020MH391)
  • 济南市“新高校20条”科研带头人工作室项目(202228124)
文献
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参考文献 引证文献
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2024年第43卷第1期
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doi: 10.14109/j.cnki.xyylc.2024.01.03
  • 接收时间：2022-05-24
  • 首发时间：2026-03-19
  • 出版时间：2024-01-25
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  • 收稿日期：2022-05-24
  • 录用日期：2023-08-21
基金
济南市科技创新发展计划(202134068)
山东省自然科学基金面上项目(ZR2020MH391)
济南市“新高校20条”科研带头人工作室项目(202228124)
作者信息
    1.山东中医药大学第一临床医学院，山东 济南　250014
    2.山东中医药大学附属医院 麻醉科，山东 济南　250014

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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
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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