Application of esketamine for postoperative analgesia in cesarean section: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LIANG Simin ¹ , DU Yu ² , JIA Dong ¹ , TU Faping ¹ ,  WANG Ji ¹

1. Department of Anesthesiology, the Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, P. R. China;
2. Department of Anesthesiology, the Second Clinical Medical College of North Sichuan Medical College, Nanchong Central Hospital, Nanchong 637000, P. R. China;

Corresponding author：

WANG Ji, Email: wangjinsmc@sina.com

Keywords：

Esketamine; Cesarean section; Randomized controlled trial; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.202202005

Video：

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Objective To systemically review the clinical application of esketamine for postoperative analgesia in cesarean section. Methods Databases including CNKI, VIP, WanFang Data, PubMed, EMbase, Web of Science, and The Cochrane Library were searched for randomized controlled trials (RCTs) on esketamine in cesarean section from inception to January 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.4 software. Results A total of 16 RCTs involving 1 715 cesarean section patients were included. The results of meta-analysis showed that esketamine decreased the patients’ visual analog scale scores after surgery (MD=−0.67, 95%CI −0.86 to −0.49, P<0.000 01) and reduced the need for analgesics for 48 hours after surgery (MD=−2.38, 95%CI −3.15 to −1.62, P<0.000 01) compared with the control drugs (such as opioids, ropivacaine, and normal saline), without increasing adverse reactions such as nausea and vomiting (RR=0.84, 95%CI 0.62 to 1.12, P=0.23), hallucinations (RR=3.00, 95%CI 0.37 to 24.43, P=0.30), drowsiness (RR=1.49, 95%CI 0.16 to 13.99, P=0.73), itching (RR=1.05, 95%CI 0.79 to 1.41, P=0.72), hypotension (RR=0.31, 95%CI 0.04 to 2.40, P=0.26), bradycardia (RR=0.40, 95%CI 0.01 to 11.24, P=0.59), and dizziness (RR=2.24, 95%CI 0.63 to 7.94, P=0.21). Compared with the control drugs, esketamine extended the operation time (MD=2.23, 95%CI 1.73 to 2.74, P<0.000 01), accelerated heart rate (MD=1.31, 95%CI 0.25 to 2.37, P=0.02), and increased the mean arterial pressure (MD=3.88, 95%CI 0.19 to 7.56, P=0.04) during surgery. Additionally, esketamine improved the Apgar score of neonates (MD=0.45, 95%CI 0.26 to 0.63, P<0.000 01) and the Edinburgh postnatal depression scale score of mothers (MD=−1.12, 95%CI −1.87 to −0.55, P=0.000 3), having no effects on the cord blood pH of neonates (MD=0.03, 95%CI −0.01 to 0.07, P=0.14). Conclusion Esketamine has certain advantages when used for postoperative analgesia in cesarean section. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to further verify the above conclusion.

Citation： LIANG Simin, DU Yu, JIA Dong, TU Faping, WANG Ji. Application of esketamine for postoperative analgesia in cesarean section: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2022, 22(6): 667-675. doi: 10.7507/1672-2531.202202005 Copy

1.	Yan J, Wang L, Yang Y, et al. The trend of caesarean birth rate changes in China after universal two-child policy era: a population-based study in 2013-2018. BMC Med, 2020, 18(1): 249.
2.	Beyene MG, Zemedu TG, Gebregiorgis AH, et al. Cesarean delivery rates, hospital readiness and quality of clinical management in Ethiopia: national results from two cross-sectional emergency obstetric and newborn care assessments. BMC Pregnancy Childbirth, 2021, 21(1): 571.
3.	Wisner KL, Stika CS, Clark CT. Double duty: does epidural labor analgesia reduce both pain and postpartum depression. Anesth Analg, 2014, 119(2): 219-221.
4.	Higgins JPT, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of interventions version 6.2. Cochrane, 2022. Available at: www. training. cochrane. org/handbook.
5.	杨帆. 剖宫产术后镇痛中应用舒芬太尼复合小剂量艾斯氯胺酮的应用效果. 中国保健营养, 2020, 30(31): 62.
6.	Suppa E, Valente A, Catarci S, et al. A study of low-dose S-ketamine infusion as "preventive" pain treatment for cesarean section with spinal anesthesia: benefits and side effects. Minerva Anestesiol, 2012, 78(7): 774-781.
7.	Unlugenc H, Ozalevli M, Gunes Y, et al. A double-blind comparison of intrathecal S(+) ketamine and fentanyl combined with bupivacaine 0. 5% for caesarean delivery. Eur J Anaesthesiol, 2006, 23(12): 1018-1024.
8.	Adams HA, Meyer P, Stoppa A, et al. Anaesthesia for caesarean section. Comparison of two general anaesthetic regimens and spinal anaesthesia. Anaesthesist, 2003, 52(1): 23-32.
9.	刘洋, 李熊刚. 艾司氯胺酮复合氢吗啡酮对剖宫产术后镇痛及产后抑郁的影响. 山东医药, 2021, 61(19): 84-87.
10.	杨梅, 卞新荣. 艾斯氯胺酮对剖宫产产妇术后镇痛效果及呼吸循环功能的影响. 齐齐哈尔医学院学报, 2021, 42(10): 856-859.
11.	顾盼, 姜秀丽, 杜伯祥, 等. 艾司氯胺酮PCIA对剖宫产术孕产妇产后抑郁症的影响. 中华麻醉学杂志, 2021, 41(3): 274-277.
12.	常俊晓. 艾司氯胺酮复合硬膜外麻醉用于剖宫产术的临床效果研究. 母婴世界, 2021, (14): 18,20.
13.	徐敏杰. 艾司氯胺酮在产科紧急剖宫产中的应用研究. 黑龙江医药, 2021, 34(4): 879-881.
14.	陶应军, 曾毅, 彭玲. 微量泵注低剂量艾司氯胺酮对剖宫产产妇产后抑郁的影响观察. 医药前沿, 2021, 11(17): 6-8.
15.	郭杰, 杨春云, 田静. 小剂量艾司氯胺酮复合舒芬太尼用于剖宫产术后自控静脉镇痛的效果. 中国医药, 2021, 16(12): 1859-1863.
16.	邢婧, 杨沫, 王希. 艾司氯胺酮在肥胖孕妇剖宫产全麻中的应用研究. 中国计划生育和妇产科, 2021, 13(11): 69-72.
17.	严佳敏, 刘先保. 联合应用艾司氯胺酮和舒芬太尼的剖宫产术后镇痛效果及抗抑郁作用. 江苏医药, 2021, 47(11): 1132-1135,1139.
18.	周敏. 艾司氯胺酮在剖宫产术全麻中的应用. 北方药学, 2021, 18(5): 181-182.
19.	Zhang X, Wang J, An XH, et al. Optimum dose of spinal ropivacaine with or without single intravenous bolus of S-ketamine during elective cesarean delivery: a randomized, double-blind, sequential dose-finding study. BMC Pregnancy Childbirth, 2021, 21(1): 746.
20.	Wang Y, Zhang Q, Dai X, et al. Effect of low-dose esketamine on pain control and postpartum depression after cesarean section: a retrospective cohort study. Ann Palliat Med, 2022, 11(1): 45-57.
21.	McGrath S, Zhao X, Steele R, et al. Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis. Stat Methods Med Res, 2020, 962280219889080.
22.	李峰, 沈通桃. 围术期非阿片类镇痛药的应用进展. 系统医学, 2021, 6(2): 195-198.
23.	Mikkelsen S, Ilkjaer S, Brennum J, et al. The effect of naloxone on ketamine-induced effects on hyperalgesia and ketamine-induced side effects in humans. Anesthesiology, 1999, 90(6): 1539-1545.
24.	Thiruvenkatarajan V, Wood R, Watts R, et al. The intraoperative use of non-opioid adjuvant analgesic agents: a survey of anaesthetists in Australia and New Zealand. BMC Anesthesiol, 2019, 19(1): 188.
25.	韦珊珊, 韦宁. 剖宫产术后镇痛的研究进展. 中国临床新医学, 2019, 12(7): 812-815.
26.	Raeder JC, Stenseth LB. Ketamine: a new look at an old drug. Curr Opin Anaesthesiol, 2000, 13(4): 463-468.
27.	汪芸荟, 张中军, 郑子豪. 右旋氯胺酮的临床应用研究进展. 今日药学, 2021, 31(10): 797-800.
28.	Trimmel H, Helbok R, Staudinger T, et al. S(+)-ketamine: current trends in emergency and intensive care medicine. Wien Klin Wochenschr, 2018, 130(9-10): 356-366.
29.	Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Focus (Am Psychiatr Publ), 2019, 17(1): 55-65.
30.	Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry, 2018, 75(2): 139-148.
31.	Ihmsen H, Geisslinger G, Schüttler J. Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine. Clin Pharmacol Ther, 2001, 70(5): 431-438.
32.	王莹莹, 赵璇. 右旋氯胺酮药理机制和药物动力学特点及临床应用的研究进展. 中华实用诊断与治疗杂志, 2019, 33(7): 724-728.
33.	李新, 余小玉, 司文凤. 氯胺酮对新生儿Apgar评分的影响. 河南医药信息, 2002, (19): 34-35.
34.	刘丝濛, 岳云. 右氯胺酮的药理学特点和临床应用. 国际麻醉学与复苏杂志, 2016, 37(1): 62-66,71.
35.	余乐, 王清秀. 麻醉药抗抑郁作用的研究进展. 同济大学学报(医学版), 2021, 42(4): 574-580.
36.	赵文莉, 邱妍, 李玮玲, 等. 一种新机制抗抑郁药: 艾司氯胺酮. 中国新药与临床杂志, 2019, 38(10): 585-588.
37.	Machado C, Lacerda ALT, Bressan RA, et al. Esketamine for postpartum suicidality. Biol Psychiatry, 2021, 89(6): e35-e36.

1. Yan J, Wang L, Yang Y, et al. The trend of caesarean birth rate changes in China after universal two-child policy era: a population-based study in 2013-2018. BMC Med, 2020, 18(1): 249.
2. Beyene MG, Zemedu TG, Gebregiorgis AH, et al. Cesarean delivery rates, hospital readiness and quality of clinical management in Ethiopia: national results from two cross-sectional emergency obstetric and newborn care assessments. BMC Pregnancy Childbirth, 2021, 21(1): 571.
3. Wisner KL, Stika CS, Clark CT. Double duty: does epidural labor analgesia reduce both pain and postpartum depression. Anesth Analg, 2014, 119(2): 219-221.
4. Higgins JPT, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of interventions version 6.2. Cochrane, 2022. Available at: www. training. cochrane. org/handbook.
5. 杨帆. 剖宫产术后镇痛中应用舒芬太尼复合小剂量艾斯氯胺酮的应用效果. 中国保健营养, 2020, 30(31): 62.
6. Suppa E, Valente A, Catarci S, et al. A study of low-dose S-ketamine infusion as "preventive" pain treatment for cesarean section with spinal anesthesia: benefits and side effects. Minerva Anestesiol, 2012, 78(7): 774-781.
7. Unlugenc H, Ozalevli M, Gunes Y, et al. A double-blind comparison of intrathecal S(+) ketamine and fentanyl combined with bupivacaine 0. 5% for caesarean delivery. Eur J Anaesthesiol, 2006, 23(12): 1018-1024.
8. Adams HA, Meyer P, Stoppa A, et al. Anaesthesia for caesarean section. Comparison of two general anaesthetic regimens and spinal anaesthesia. Anaesthesist, 2003, 52(1): 23-32.
9. 刘洋, 李熊刚. 艾司氯胺酮复合氢吗啡酮对剖宫产术后镇痛及产后抑郁的影响. 山东医药, 2021, 61(19): 84-87.
10. 杨梅, 卞新荣. 艾斯氯胺酮对剖宫产产妇术后镇痛效果及呼吸循环功能的影响. 齐齐哈尔医学院学报, 2021, 42(10): 856-859.
11. 顾盼, 姜秀丽, 杜伯祥, 等. 艾司氯胺酮PCIA对剖宫产术孕产妇产后抑郁症的影响. 中华麻醉学杂志, 2021, 41(3): 274-277.
12. 常俊晓. 艾司氯胺酮复合硬膜外麻醉用于剖宫产术的临床效果研究. 母婴世界, 2021, (14): 18,20.
13. 徐敏杰. 艾司氯胺酮在产科紧急剖宫产中的应用研究. 黑龙江医药, 2021, 34(4): 879-881.
14. 陶应军, 曾毅, 彭玲. 微量泵注低剂量艾司氯胺酮对剖宫产产妇产后抑郁的影响观察. 医药前沿, 2021, 11(17): 6-8.
15. 郭杰, 杨春云, 田静. 小剂量艾司氯胺酮复合舒芬太尼用于剖宫产术后自控静脉镇痛的效果. 中国医药, 2021, 16(12): 1859-1863.
16. 邢婧, 杨沫, 王希. 艾司氯胺酮在肥胖孕妇剖宫产全麻中的应用研究. 中国计划生育和妇产科, 2021, 13(11): 69-72.
17. 严佳敏, 刘先保. 联合应用艾司氯胺酮和舒芬太尼的剖宫产术后镇痛效果及抗抑郁作用. 江苏医药, 2021, 47(11): 1132-1135,1139.
18. 周敏. 艾司氯胺酮在剖宫产术全麻中的应用. 北方药学, 2021, 18(5): 181-182.
19. Zhang X, Wang J, An XH, et al. Optimum dose of spinal ropivacaine with or without single intravenous bolus of S-ketamine during elective cesarean delivery: a randomized, double-blind, sequential dose-finding study. BMC Pregnancy Childbirth, 2021, 21(1): 746.
20. Wang Y, Zhang Q, Dai X, et al. Effect of low-dose esketamine on pain control and postpartum depression after cesarean section: a retrospective cohort study. Ann Palliat Med, 2022, 11(1): 45-57.
21. McGrath S, Zhao X, Steele R, et al. Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis. Stat Methods Med Res, 2020, 962280219889080.
22. 李峰, 沈通桃. 围术期非阿片类镇痛药的应用进展. 系统医学, 2021, 6(2): 195-198.
23. Mikkelsen S, Ilkjaer S, Brennum J, et al. The effect of naloxone on ketamine-induced effects on hyperalgesia and ketamine-induced side effects in humans. Anesthesiology, 1999, 90(6): 1539-1545.
24. Thiruvenkatarajan V, Wood R, Watts R, et al. The intraoperative use of non-opioid adjuvant analgesic agents: a survey of anaesthetists in Australia and New Zealand. BMC Anesthesiol, 2019, 19(1): 188.
25. 韦珊珊, 韦宁. 剖宫产术后镇痛的研究进展. 中国临床新医学, 2019, 12(7): 812-815.
26. Raeder JC, Stenseth LB. Ketamine: a new look at an old drug. Curr Opin Anaesthesiol, 2000, 13(4): 463-468.
27. 汪芸荟, 张中军, 郑子豪. 右旋氯胺酮的临床应用研究进展. 今日药学, 2021, 31(10): 797-800.
28. Trimmel H, Helbok R, Staudinger T, et al. S(+)-ketamine: current trends in emergency and intensive care medicine. Wien Klin Wochenschr, 2018, 130(9-10): 356-366.
29. Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Focus (Am Psychiatr Publ), 2019, 17(1): 55-65.
30. Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry, 2018, 75(2): 139-148.
31. Ihmsen H, Geisslinger G, Schüttler J. Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine. Clin Pharmacol Ther, 2001, 70(5): 431-438.
32. 王莹莹, 赵璇. 右旋氯胺酮药理机制和药物动力学特点及临床应用的研究进展. 中华实用诊断与治疗杂志, 2019, 33(7): 724-728.
33. 李新, 余小玉, 司文凤. 氯胺酮对新生儿Apgar评分的影响. 河南医药信息, 2002, (19): 34-35.
34. 刘丝濛, 岳云. 右氯胺酮的药理学特点和临床应用. 国际麻醉学与复苏杂志, 2016, 37(1): 62-66,71.
35. 余乐, 王清秀. 麻醉药抗抑郁作用的研究进展. 同济大学学报(医学版), 2021, 42(4): 574-580.
36. 赵文莉, 邱妍, 李玮玲, 等. 一种新机制抗抑郁药: 艾司氯胺酮. 中国新药与临床杂志, 2019, 38(10): 585-588.
37. Machado C, Lacerda ALT, Bressan RA, et al. Esketamine for postpartum suicidality. Biol Psychiatry, 2021, 89(6): e35-e36.

Chinese Journal of Evidence-Based Medicine

Application of esketamine for postoperative analgesia in cesarean section: a meta-analysis

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