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Article(id=1241768180314603966, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241768176522957402, articleNumber=null, orderNo=null, doi=10.14109/j.cnki.xyylc.2024.05.08, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1671033600000, receivedDateStr=2022-12-15, revisedDate=null, revisedDateStr=null, acceptedDate=1702396800000, acceptedDateStr=2023-12-13, onlineDate=1773990205124, onlineDateStr=2026-03-20, pubDate=1716566400000, pubDateStr=2024-05-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773990205124, onlineIssueDateStr=2026-03-20, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773990205124, creator=13701087609, updateTime=1773990205124, updator=13701087609, issue=Issue{id=1241768176522957402, tenantId=1146029695717560320, journalId=1205117082300743687, year='2024', volume='43', issue='5', pageStart='321', pageEnd='400', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773990204220, creator=13701087609, updateTime=1773992176593, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241776449330414547, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241768176522957402, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241776449330414548, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1241768176522957402, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=360, endPage=364, ext={EN=ArticleExt(id=1241768180616593855, articleId=1241768180314603966, tenantId=1146029695717560320, journalId=1205117082300743687, language=EN, title=Analgesic effect of low-dose esketamine combined with sufentanil after off-pump coronary artery bypass grafting, columnId=1207314218647392369, journalTitle=Chinese Journal of New Drugs and Clinical Remedies, columnName=Original Article, runingTitle=null, highlight=null, articleAbstract=
AIM

To observe the safety and efficacy of patient-controlled intravenous analgesia （PCIA） with low-dose esketamine combined with sufentanil after off-pump coronary artery bypass grafting （OPCABG）.

METHODS

Sixty patients undergoing OPCABG under general anesthesia were randomly divided into group S and group ES, with 30 patients in each group. The anesthesia induction and maintenance programs of the two groups were the same. Immediately after the operation, the group ES was injected with esketamine 0.05 mg·kg-1 intravenously, followed by continuous infusion of esketamine 0.5 µg·kg-1·min-1 for 72 h with equal volume sodium chloride injection in the group S. Then PCIA（ sufentanil 1.8 µg·kg-1 in the group ES, sufentanil 3 µg·kg-1 in the group S） was performed immediately for 72 h. The opioid dosage,analgesia satisfaction, effective pressing times of analgesia pump, rescue analgesia rate, pain and sedation score and vital signs in the two groups within 72 h after operation were observed. The time of awakening, extubation and exhaust after operation was recorded, the level of serum troponin was detected on the 4th day after operation, and the adverse drug reactions were observed within 72 h after operation.

RESULTS

Compared with the group S, the dosage of sufentanil and morphine decreased, the satisfaction of analgesia was higher, the rate of rescue analgesia was lower, and the Prince-Henry pain score at 12, 24, 48 and 72 h after operation in the group ES was significantly lower than that in the group S（ P<0.05）.There was no significant difference in awakening time and Ramsay sedation score, heart rate, mean arterial pressure and central venous pressure between the two groups at 6, 12, 24, 48 and 72 h after operation. There was no significant difference in the level of serum troponin between the two groups on the 4th day after operation（ P>0.05）. Within 72 h after operation,the incidence of nausea, vomiting and hypoxemia in the group ES was significantly lower than that in the group S（ P<0.05）,and there was no significant difference in the incidence of hypertension and skin pruritus（ P>0.05）.

CONCLUSION

Low-dose esketamine combined with sufentanil PCIA can be safely used after OPCABG, and can significantly reduce the dosage of sufentanil and improve the analgesia satisfaction of patients.

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目的

观察小剂量艾司氯胺酮复合舒芬太尼患者自控静脉镇痛（PCIA）在非体外循环冠状动脉旁路移植术（OPCABG）后镇痛应用的安全性和有效性。

方法

选取全身麻醉下行OPCABG患者60例，随机分为S组和ES组，每组30例，2组患者麻醉诱导及维持方案一致。术毕即刻ES组给予艾司氯胺酮0.05 mg·kg-1静脉注射，后以0.5 µg·kg-1·min-1持续泵注72 h，S组给予等容量氯化钠注射液。随后2组即刻行PCIA（ES组舒芬太尼1.8µg·kg-1，S组舒芬太尼3 µg·kg-1） 72 h。观察2组术后72 h内阿片类药物用量、镇痛满意度、镇痛泵有效按压次数和补救镇痛率，以及疼痛和镇静评分、生命体征指标的变化。记录术后苏醒、拔管和排气时间，检测术后第4日血肌钙蛋白Ⅰ水平，观察术后72 h内药物不良反应发生情况。

结果

与S组比较，ES组术后舒芬太尼和吗啡用量减少，镇痛满意度高、补救镇痛率低，术后12、24、48、72 h的Prince-Henry疼痛评分低，差异均有显著意义（P<0.05）。2组苏醒时间和术后6、12、24、48、72 h的Ramsay镇静评分、心率、平均动脉压、中心静脉压比较，差异均无显著意义（P>0.05）。术后第4日血肌钙蛋白Ⅰ水平组间比较无显著差异（P>0.05）。术后72 h内，ES组恶心、呕吐、低氧血症发生率显著低于S组（P<0.05），高血压、皮肤瘙痒等发生率比较无显著差异（P>0.05）。

结论

小剂量艾司氯胺酮复合舒芬太尼PCIA可安全用于OPCABG术后，且可显著减少舒芬太尼用量，提高患者镇痛满意度。

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李星，男，住院医师，硕士，主要从事围术期器官功能保护的研究，Phn: 86-18840106939，E-mail:

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李星，男，住院医师，硕士，主要从事围术期器官功能保护的研究，Phn: 86-18840106939，E-mail:

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李星，男，住院医师，硕士，主要从事围术期器官功能保护的研究，Phn: 86-18840106939，E-mail:

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Eur J Anaesthesiol, 2005, 22（3）: 215-221., articleTitle=Ketamine enantiomers differentially relax isolated coronary artery rings, refAbstract=null), Reference(id=1241768193878983428, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, doi=null, pmid=null, pmcid=null, year=1999, volume=90, issue=5, pageStart=1363, pageEnd=1371, url=null, language=null, rfNumber=[12], rfOrder=13, authorNames=KUNST G, MARTIN E, GRAF BM, journalName=Anesthesiology, refType=null, unstructuredReference=KUNST G, MARTIN E, GRAF BM, et al. Actions of ketamine and its isomers on contractility and calcium transients in human myocardium [J]. 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Comparison of S-（+）-ketamine- with sufentanil-based anaesthesia for elective coronary artery bypass graft surgery: effect on troponin T levels [J].Br J Anaesth, 2008, 100（6）: 765-771., articleTitle=Comparison of S-（+）-ketamine- with sufentanil-based anaesthesia for elective coronary artery bypass graft surgery: effect on troponin T levels, refAbstract=null), Reference(id=1241768194176779025, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, doi=null, pmid=null, pmcid=null, year=2018, volume=120, issue=5, pageStart=1117, pageEnd=1127, url=null, language=null, rfNumber=[14], rfOrder=15, authorNames=JONKMAN K, van RIJNSOEVER E, OLOFSEN E, journalName=Br J Anaesth, refType=null, unstructuredReference=JONKMAN K, van RIJNSOEVER E, OLOFSEN E, et al.Esketamine counters opioid-induced respiratory depression [J].Br J Anaesth, 2018, 120（5）: 1117-1127., articleTitle=Esketamine counters opioid-induced respiratory depression, refAbstract=null), Reference(id=1241768194394882839, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, doi=null, pmid=null, pmcid=null, year=2011, volume=25, issue=6, pageStart=1163, pageEnd=1178, url=null, language=null, rfNumber=[15], rfOrder=16, authorNames=MAZZEFFI M, KHELEMSKY Y, journalName=J Cardiothorac Vasc Anesth, refType=null, unstructuredReference=MAZZEFFI M, KHELEMSKY Y. 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J Affect Disord, 2021, 278: 542-555., articleTitle=Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis, refAbstract=null), Reference(id=1241768194847867685, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, doi=null, pmid=null, pmcid=null, year=2005, volume=95, issue=4, pageStart=518, pageEnd=523, url=null, language=null, rfNumber=[18], rfOrder=19, authorNames=BENRATH J, BRECHTEL C, STARK J, journalName=Br J Anaesth, refType=null, unstructuredReference=BENRATH J, BRECHTEL C, STARK J, et al. Low dose of S（+）-ketamine prevents long-term potentiation in pain pathways under strong opioid analgesia in the rat spinal cord in vivo [J]. Br J Anaesth, 2005, 95（4）: 518-523., articleTitle=Low dose of S（+）-ketamine prevents long-term potentiation in pain pathways under strong opioid analgesia in the rat spinal cord in vivo, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1241768185129665038, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, xref=1., ext=[AuthorCompanyExt(id=1241768185138053647, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, companyId=1241768185129665038, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Department of Anesthesiology, Jinzhou Central Hospital, Graduate Training Base of Jinzhou Medical University, Jinzhou LIAONING 121000, China), AuthorCompanyExt(id=1241768185146442256, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, companyId=1241768185129665038, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.锦州医科大学研究生培养基地锦州市中心医院　麻醉科，辽宁　锦州　121000)]), AuthorCompany(id=1241768185289048599, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, xref=2., ext=[AuthorCompanyExt(id=1241768185297437208, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, companyId=1241768185289048599, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.Department of Anesthesiology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou LIAONING 121000, China), AuthorCompanyExt(id=1241768185305825817, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, companyId=1241768185289048599, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.锦州医科大学附属第一医院　麻醉科，辽宁　锦州　121000)])], figs=[ArticleFig(id=1241768187478475394, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
指标S组ES组
性别/例 男2221
女78
年龄/岁63.9±10.263.5±7.2
体重指数/kg·m-224.9±2.224.6±2.2
ASA分级/例 Ⅱ级21
Ⅲ级2728
麻醉时长/min207.4±22.2204.8±23.4
手术时长/min164.0±21.0157.2±22.1
), ArticleFig(id=1241768187587527304, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, language=CN, label=表1, caption=

患者一般情况组间比较

, figureFileSmall=null, figureFileBig=null, tableContent=
指标S组ES组
性别/例 男2221
女78
年龄/岁63.9±10.263.5±7.2
体重指数/kg·m-224.9±2.224.6±2.2
ASA分级/例 Ⅱ级21
Ⅲ级2728
麻醉时长/min207.4±22.2204.8±23.4
手术时长/min164.0±21.0157.2±22.1
), ArticleFig(id=1241768189185557138, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
指标S组ES组
Prince-Henry疼痛评分
术后6 h0（1）0（0）a
术后12 h1（2）0（0）b
术后24 h1（2）0（1）b
术后48 h1（2）0（0）b
术后72 h1（2）0（1）b
Ramsay镇静评分
术后6 h3（1）3（1）a
术后12 h2（1）2（0）a
术后24 h2（0）2（0）a
术后48 h2（0）2（0）a
术后72 h2（0）2（0）a
舒芬太尼用量/µg164.0±25.890.9±14.4c
吗啡用量/mg7.6±9.11.4±4.4b
镇痛满意度/%16（55）27（93）b
补救镇痛率/%10（34）3（10）b
镇痛泵有效按压次数1（3）0（1）c
), ArticleFig(id=1241768189344940694, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, language=CN, label=表2, caption=

镇痛和镇静效果组间比较

, figureFileSmall=null, figureFileBig=null, tableContent=
指标S组ES组
Prince-Henry疼痛评分
术后6 h0（1）0（0）a
术后12 h1（2）0（0）b
术后24 h1（2）0（1）b
术后48 h1（2）0（0）b
术后72 h1（2）0（1）b
Ramsay镇静评分
术后6 h3（1）3（1）a
术后12 h2（1）2（0）a
术后24 h2（0）2（0）a
术后48 h2（0）2（0）a
术后72 h2（0）2（0）a
舒芬太尼用量/µg164.0±25.890.9±14.4c
吗啡用量/mg7.6±9.11.4±4.4b
镇痛满意度/%16（55）27（93）b
补救镇痛率/%10（34）3（10）b
镇痛泵有效按压次数1（3）0（1）c
), ArticleFig(id=1241768189487547035, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
指标S组ES组
HR/次·min-1
术后6 h83.4±4.583.5±4.7
术后12 h81.3±3.981.4±3.9
术后24 h81.1±3.081.0±3.4
术后48 h78.6±3.378.4±2.4
术后72 h77.4±2.977.5±3.3
MAP/mmHg
术后6 h100.1±9.3100.3±8.0
术后12h 99.7±6.3100.0±6.6
术后24 h100.1±5.499.9±6.1
术后48 h95.1±4.795.3±4.9
术后72 h94.3±4.995.1±5.2
CVP/cmH2O
术后6 h5（2）5（2）
术后12 h6（1）6（1）
术后24 h6（1）6（1）
术后48 h6（2）6（0）
术后72 h6（1）6（1）
), ArticleFig(id=1241768189667902112, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, language=CN, label=表3, caption=

循环指标组间比较

, figureFileSmall=null, figureFileBig=null, tableContent=
指标S组ES组
HR/次·min-1
术后6 h83.4±4.583.5±4.7
术后12 h81.3±3.981.4±3.9
术后24 h81.1±3.081.0±3.4
术后48 h78.6±3.378.4±2.4
术后72 h77.4±2.977.5±3.3
MAP/mmHg
术后6 h100.1±9.3100.3±8.0
术后12h 99.7±6.3100.0±6.6
术后24 h100.1±5.499.9±6.1
术后48 h95.1±4.795.3±4.9
术后72 h94.3±4.995.1±5.2
CVP/cmH2O
术后6 h5（2）5（2）
术后12 h6（1）6（1）
术后24 h6（1）6（1）
术后48 h6（2）6（0）
术后72 h6（1）6（1）
), ArticleFig(id=1241768189865034408, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
不良反应S组ES组
低血压2（7）1（3）a
高血压1（3）1（3）a
恶性心律失常1（3）0（0）a
低氧血症5（17）0（0）b
恶心8（28）2（7）b
呕吐6（21）0（0）b
皮肤瘙痒5（17）4（14）a
幻觉1（3）2（7）a
), ArticleFig(id=1241768190208967347, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1241768180314603966, language=CN, label=表4, caption=

术后不良反应发生率组间比较

, figureFileSmall=null, figureFileBig=null, tableContent=
不良反应S组ES组
低血压2（7）1（3）a
高血压1（3）1（3）a
恶性心律失常1（3）0（0）a
低氧血症5（17）0（0）b
恶心8（28）2（7）b
呕吐6（21）0（0）b
皮肤瘙痒5（17）4（14）a
幻觉1（3）2（7）a
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小剂量艾司氯胺酮复合舒芬太尼在非体外循环冠状动脉旁路移植术后的镇痛作用
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李星 1 , 王昊 2
中国新药与临床杂志 | 论著 2024,43(5): 360-364
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中国新药与临床杂志 | 论著 2024, 43(5): 360-364
小剂量艾司氯胺酮复合舒芬太尼在非体外循环冠状动脉旁路移植术后的镇痛作用
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李星1 , 王昊2
作者信息
  • 1.锦州医科大学研究生培养基地锦州市中心医院　麻醉科，辽宁　锦州　121000
  • 2.锦州医科大学附属第一医院　麻醉科，辽宁　锦州　121000

    • 李星，男，住院医师，硕士，主要从事围术期器官功能保护的研究，Phn: 86-18840106939，E-mail:

Analgesic effect of low-dose esketamine combined with sufentanil after off-pump coronary artery bypass grafting
Xing LI1 , Hao WANG2
Affiliations
  • 1.Department of Anesthesiology, Jinzhou Central Hospital, Graduate Training Base of Jinzhou Medical University, Jinzhou LIAONING 121000, China
  • 2.Department of Anesthesiology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou LIAONING 121000, China
出版时间: 2024-05-25 doi: 10.14109/j.cnki.xyylc.2024.05.08
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摘要
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目的

观察小剂量艾司氯胺酮复合舒芬太尼患者自控静脉镇痛（PCIA）在非体外循环冠状动脉旁路移植术（OPCABG）后镇痛应用的安全性和有效性。

方法

选取全身麻醉下行OPCABG患者60例，随机分为S组和ES组，每组30例，2组患者麻醉诱导及维持方案一致。术毕即刻ES组给予艾司氯胺酮0.05 mg·kg-1静脉注射，后以0.5 µg·kg-1·min-1持续泵注72 h，S组给予等容量氯化钠注射液。随后2组即刻行PCIA（ES组舒芬太尼1.8µg·kg-1，S组舒芬太尼3 µg·kg-1） 72 h。观察2组术后72 h内阿片类药物用量、镇痛满意度、镇痛泵有效按压次数和补救镇痛率，以及疼痛和镇静评分、生命体征指标的变化。记录术后苏醒、拔管和排气时间，检测术后第4日血肌钙蛋白Ⅰ水平，观察术后72 h内药物不良反应发生情况。

结果

与S组比较，ES组术后舒芬太尼和吗啡用量减少，镇痛满意度高、补救镇痛率低，术后12、24、48、72 h的Prince-Henry疼痛评分低，差异均有显著意义（P<0.05）。2组苏醒时间和术后6、12、24、48、72 h的Ramsay镇静评分、心率、平均动脉压、中心静脉压比较，差异均无显著意义（P>0.05）。术后第4日血肌钙蛋白Ⅰ水平组间比较无显著差异（P>0.05）。术后72 h内，ES组恶心、呕吐、低氧血症发生率显著低于S组（P<0.05），高血压、皮肤瘙痒等发生率比较无显著差异（P>0.05）。

结论

小剂量艾司氯胺酮复合舒芬太尼PCIA可安全用于OPCABG术后，且可显著减少舒芬太尼用量，提高患者镇痛满意度。

艾司氯胺酮  /  舒芬太尼  /  冠状动脉旁路移植术，非体外循环  /  术后镇痛
AIM

To observe the safety and efficacy of patient-controlled intravenous analgesia （PCIA） with low-dose esketamine combined with sufentanil after off-pump coronary artery bypass grafting （OPCABG）.

METHODS

Sixty patients undergoing OPCABG under general anesthesia were randomly divided into group S and group ES, with 30 patients in each group. The anesthesia induction and maintenance programs of the two groups were the same. Immediately after the operation, the group ES was injected with esketamine 0.05 mg·kg-1 intravenously, followed by continuous infusion of esketamine 0.5 µg·kg-1·min-1 for 72 h with equal volume sodium chloride injection in the group S. Then PCIA（ sufentanil 1.8 µg·kg-1 in the group ES, sufentanil 3 µg·kg-1 in the group S） was performed immediately for 72 h. The opioid dosage,analgesia satisfaction, effective pressing times of analgesia pump, rescue analgesia rate, pain and sedation score and vital signs in the two groups within 72 h after operation were observed. The time of awakening, extubation and exhaust after operation was recorded, the level of serum troponin was detected on the 4th day after operation, and the adverse drug reactions were observed within 72 h after operation.

RESULTS

Compared with the group S, the dosage of sufentanil and morphine decreased, the satisfaction of analgesia was higher, the rate of rescue analgesia was lower, and the Prince-Henry pain score at 12, 24, 48 and 72 h after operation in the group ES was significantly lower than that in the group S（ P<0.05）.There was no significant difference in awakening time and Ramsay sedation score, heart rate, mean arterial pressure and central venous pressure between the two groups at 6, 12, 24, 48 and 72 h after operation. There was no significant difference in the level of serum troponin between the two groups on the 4th day after operation（ P>0.05）. Within 72 h after operation,the incidence of nausea, vomiting and hypoxemia in the group ES was significantly lower than that in the group S（ P<0.05）,and there was no significant difference in the incidence of hypertension and skin pruritus（ P>0.05）.

CONCLUSION

Low-dose esketamine combined with sufentanil PCIA can be safely used after OPCABG, and can significantly reduce the dosage of sufentanil and improve the analgesia satisfaction of patients.

esketamine  /  sufentanil  /  coronary artery bypass, off-pump  /  postoperative analgesia
李星, 王昊. 小剂量艾司氯胺酮复合舒芬太尼在非体外循环冠状动脉旁路移植术后的镇痛作用. 中国新药与临床杂志, 2024 , 43 (5) : 360 -364 . DOI: 10.14109/j.cnki.xyylc.2024.05.08
Xing LI, Hao WANG. Analgesic effect of low-dose esketamine combined with sufentanil after off-pump coronary artery bypass grafting[J]. Chinese Journal of New Drugs and Clinical Remedies, 2024 , 43 (5) : 360 -364 . DOI: 10.14109/j.cnki.xyylc.2024.05.08
正文
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随着老龄化进展，冠心病现已成为我国重要的公共卫生问题［1］。非体外循环下冠状动脉旁路移植术（OPCABG）是冠心病血运重建的主要方法之一，但其术后疼痛不仅会导致血流动力学不稳定及冠状动脉痉挛，还会影响正常咳嗽能力和呼吸力学，从而增加术后心肺不良反应发生率［2］。目前术后镇痛药物仍以阿片类药物为主，但高剂量的阿片类药物除了会引起恶心、呕吐、皮肤瘙痒等不良反应外，还会引起严重的呼吸和循环抑制［3］。艾司氯胺酮是氯胺酮的外旋异构体，主要通过非竞争性拮抗N-甲基-D-天冬氨酸（NMDA）受体发挥镇静、镇痛作用，效能是氯胺酮的两倍，麻醉镇痛效果更佳，精神类不良反应更少［4］。有研究显示，术后应用艾司氯胺酮能减少阿片类药物用量且有更高的镇痛满意度，同时不增加不良反应发生率［5］。本研究旨在观察小剂量艾司氯胺酮持续泵注复合舒芬太尼患者自控静脉镇痛（PCIA）在OPCABG术后应用的安全性和有效性。
资料与方法
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病例选择和分组
选取锦州医科大学附属第一医院2021年8月至2022年9月择期全身麻醉（全麻）下行前正中线切口OPCABG患者60例，年龄18~84岁、体重指数（BMI）18.5~27.9 kg·m-2、ASA分级Ⅱ或Ⅲ级、纽约心功能分级（NYHA）Ⅱ级。排除标准：有精神病史，长期服用镇静、镇痛药物史，甲状腺功能亢进，肥厚梗阻型心肌病，心室率控制不佳的心房颤动。采用随机数字表法将患者分为S组（舒芬太尼组）和ES组（艾司氯胺酮复合舒芬太尼组），每组30例。本研究经锦州医科大学附属第一医院伦理委员会审核通过（202271-2），患者或家属签署知情同意书。所有手术均由同一组医师实施，术前进行镇痛宣教。
麻醉方法
术日晨予患者咪达唑仑15 mg口服，入手术室前30 min肌内注射（肌注）吗啡10 mg。入室后常规监测心率（HR）、脉搏氧饱和度（SpO2）、心电图和脑电双频指数（BIS），开放外周静脉通路，局部麻醉下桡动脉穿刺持续监测有创血压（IBP）。麻醉诱导：静脉注射（静注）依托咪酯0.15 mg·kg-1，咪达唑仑4 mg，顺阿曲库胺2 mg·kg-1，舒芬太尼2 µg·kg-1，气管插管后行机械通气及右侧颈内静脉置管并监测中心静脉压 （CVP）。麻醉维持：吸入1%七氟烷，静脉持续泵注丙泊酚3 mg·kg-1·h-1、右美托咪定0.4 µg·kg-1·min-1、顺阿曲库胺2 µg·kg-1·min-1，间断静注舒芬太尼。术中维持BIS在45~60、平均动脉压（MAP）在60~100 mmHg、HR波动幅度在基线±20%内。术毕即刻，ES组静注艾司氯胺酮（江苏恒瑞医药股份有限公司，批准文号：国药准字H20193336）0.05 mg·kg-1（浓度 1 mg·mL-1，给药时间30 s）后以0.5 µg·kg-1·min-1（浓度1 mg·mL-1）持续泵注72 h，S组静注等容量氯化钠注射液。随后2组即刻行PCIA，ES组给予舒芬太尼（宜昌人福药业责任有限公司，批准文号：国药准字H20054171）1.8 µg·kg-1，S组给予舒芬太尼3 µg·kg-1，均用氯化钠注射液稀释至100 mL，背景剂量1 mL·h-1，追加剂量2 mL，锁定时间15 min。当Prince-Henry疼痛评分（0分：咳嗽时无痛；1分：咳嗽时才有疼痛发生；2分：深呼吸时有疼痛，安静时无疼痛；3分：静息状态下即有疼痛，但较轻可忍受；4分：静息状态下即有剧烈疼痛，难以忍受）>4分且按压一次镇痛泵而疼痛持续不缓解时，肌注吗啡10 mg做补救镇痛。
观察指标
记录麻醉时长和手术时长，术后72 h内2组的舒芬太尼和吗啡用量、补救镇痛率、镇痛泵有效按压次数，撤镇痛泵后评估镇痛满意度，以患者自身主观感受为标准。评估并记录患者术后6、12、24、48、72 h的Prince-Henry疼痛评分、Ramsay镇静评分、HR、MAP和CVP。记录术后苏醒时间、拔管时间、首次排气时间，检测术后第4日血肌钙蛋白Ⅰ水平。记录术后72 h内低血压（降幅超过术前的20%）、高血压（升幅超过术前的20%）、恶性心律失常、低氧血症（SpO2<90%）、恶心、呕吐、皮肤瘙痒及幻觉的发生情况。
统计学分析
采用SPSS21.0软件进行分析。正态分布的计量资料以均数±标准差表示，组间比较采用t检验；非正态分布的计量资料以中位数（M）和四分位数间距（IQR）表示，组间比较采用Mann-Whitney U检验；计数资料以例（%）表示，组间比较采用χ2检验。P<0.05为差异有显著意义。
结 果
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一般情况
研究中剔除2例患者，1例术中转体外循环下手术，1例术后发生血管麻痹综合征，最终2组各完成29例。2组性别、年龄、BMI、ASA分级、麻醉时长、手术时长比较，差异均无显著意义（P> 0.05），见表1。
镇痛和镇静效果
与S组比较，ES组术后12、24、48、72 h的疼痛评分降低（P<0.05），ES组术后各观察时点的Ramsay镇静评分略低于S组，但无显著差异（P>0.05）。与S组相比，ES组在术后72 h内舒芬太尼及吗啡用量减少，患者镇痛满意度高，补救镇痛率低，镇痛泵有效按压次数减少（P<0.05或P<0.01）。见表2。
术后苏醒、拔管及排气时间
S组苏醒时间、拔管时间、排气时间分别为（144.1±17.6）min、（217.1±27.9）min、（31.1±3.7）h，ES组分别为（139.3±18.6）min、（184.0±24.4）min、（26.2±3.5）h。与S组比较，ES组拔管时间和排气时间显著缩短（P<0.05），苏醒时间略缩短，但组间比较无显著差异（P>0.05）。
肌钙蛋白Ⅰ
术后第4日，S组肌钙蛋白Ⅰ水平为68（112） µg·L-1，ES组为60（95） µg·L-1，组间比较差异无显著意义（P>0.05）。
循环指标
各观察时间点2组的HR、MAP、CVP比较，均无显著差异（P>0.05）。见表3。
不良反应
与S组比较，ES组术后72 h内低氧血症、恶心及呕吐的发生率更低（P<0.05），高血压、低血压、恶性心律失常、皮肤瘙痒及幻觉发生率组间比较无显著差异（P>0.05）。见表4。
讨 论
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心脏术后良好的镇痛方案能减少术后并发症及不良反应的发生，既往有研究采用舒芬太尼3 µg·kg-1术后镇痛，但临床镇痛效果并不理想［6］，这可能与术中使用大量阿片类药物导致的痛觉过敏和阿片耐受有关［7］。有研究指出，给予氯胺酮0.1 ~ 0.2 mg·kg-1负荷剂量后，以1~2 µg·kg-1·min-1持续泵注能发挥其抗痛觉过敏、抗阿片耐受的作用，从而达到很好的镇痛效果［8］，而艾司氯胺酮的效能是氯胺酮的两倍，因此本研究采取小剂量艾司氯胺酮，即静注负荷剂量0.05 mg·kg-1后以0.5 µg·kg-1·min-1持续泵注。另外，有研究也表明开胸术后以艾司氯胺酮小剂量（0.015 mg·kg-1·h-1）持续泵注不仅能减少40%阿片类药物的用量，还可以减少痛觉过敏和术后谵妄的发生率［9］，因此本研究的ES组舒芬太尼用量为S组的60%，即1.8 µg·kg-1。本研究结果显示，与S组相比，ES组舒芬太尼用量减少了45%，吗啡用量减少了82%，患者镇痛满意度明显提升，PCIA按压次数也减少。术后6 h疼痛评分组间比较无显著差异，这可能与CABG术中大量长效阿片类药物的残留有关。术后12、24、48、72 h，ES组的Prince-Henry疼痛评分均低于S组，以术后12、48 h差异尤为显著，这个结果与其他研究［10］相一致。另外，本研究中ES组的补救镇痛率明显低于S组，这或许与艾司氯胺酮抑制了心脏术中大量阿片类药物使用所导致的阿片耐受有关。本研究中与S组相比，ES组各时段的Ramsay镇静评分略低、术后苏醒时间略缩短，但组间并无显著差异，可能是由于S组阿片类药物用量大于ES组所致。
艾司氯胺酮对心血管受损的患者有诸多潜在益处，如与氯胺酮相比有更强的冠状动脉扩张作用［11］，在低浓度下能增强心肌等张收缩力、等长收缩力及舒张功能，且这种作用并不经交感兴奋介导［12］，然而由于艾司氯胺酮的拟交感特点使其应用于冠心病患者仍备受争议。有研究证实，应用艾司氯胺酮麻醉诱导并不会使择期OPCABG患者术后肌钙蛋白水平升高［13］，提示麻醉剂量的艾司氯胺酮并不会增加冠心病患者围术期心肌损伤风险。本研究结果显示，2组术后各时段的MAP、HR、CVP以及术后第4日肌钙蛋白Ⅰ水平并无显著差异，也提示在CABG术后使用小剂量艾司氯胺酮并不会使患者HR及血压升高，也不会增加术后心肌损伤的风险，能安全用于冠心病患者。另外，OPCABG术后呼吸抑制也是一个临床常见且棘手的问题，有研究发现艾司氯胺酮能有效对抗阿片类药物引起的呼吸抑制［14］。本研究也发现，与S组相比，ES组患者拔管时间明显缩短，术后低氧血症发生率也显著降低，这可能不仅与艾司氯胺酮可以直接对抗阿片类药物引起的呼吸抑制有关，还与术后阿片类药物用量显著减少密不可分。2组高血压、低血压、恶性心律失常、幻觉和皮肤瘙痒的发生率无显著差异，说明2组镇痛方案均可以安全用于OPCABG术后，但ES组的恶心、呕吐发生率显著低于S组，或许与舒芬太尼和吗啡用量大量减少有关，也可能是研究样本量较少引起的误差。ES组排气时间明显早于S组，这有利于患者术后快速康复。
综上所述，小剂量艾司氯胺酮复合舒芬太尼PCIA的镇痛方案能安全用于OPCABG术后镇痛，不仅不会增加心肌损伤、循环波动、幻觉和恶性心率失常的风险，还能显著减少术后阿片类药物的用量，实现更高的镇痛满意度和更好的镇痛效果。同时还能缩短拔管和排气时间，降低术后恶心、呕吐和低氧血症的发生率，有利于患者康复。但本试验样本量较少，且未进行长期随访，艾司氯胺酮在心脏术后的最佳用药方式及用药量仍需要进一步研究。此外，心脏术后慢性疼痛发生率高［15］，且CABG术后抑郁发生率达30%~40%［16］ ，艾司氯胺酮已被FAD批准用于治疗抑郁症［17］，且有大鼠体内实验发现，低剂量艾司氯胺酮能防止强效阿片药类物镇痛引起的脊髓疼痛通路的长期增强［18］，艾司氯胺酮能否降低心脏术后慢性疼痛、抑郁的发生率也值得探索。
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2024年第43卷第5期
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doi: 10.14109/j.cnki.xyylc.2024.05.08
  • 接收时间：2022-12-15
  • 首发时间：2026-03-20
  • 出版时间：2024-05-25
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  • 收稿日期：2022-12-15
  • 录用日期：2023-12-13
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    1.锦州医科大学研究生培养基地锦州市中心医院　麻醉科，辽宁　锦州　121000
    2.锦州医科大学附属第一医院　麻醉科，辽宁　锦州　121000
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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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