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.	楊帆. 剖宮產術后鎮痛中應用舒芬太尼復合小劑量艾斯氯胺酮的應用效果. 中國保健營養, 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.	劉洋, 李熊剛. 艾司氯胺酮復合氫嗎啡酮對剖宮產術后鎮痛及產后抑郁的影響. 山東醫藥, 2021, 61(19): 84-87.
10.	楊梅, 卞新榮. 艾斯氯胺酮對剖宮產產婦術后鎮痛效果及呼吸循環功能的影響. 齊齊哈爾醫學院學報, 2021, 42(10): 856-859.
11.	顧盼, 姜秀麗, 杜伯祥, 等. 艾司氯胺酮PCIA對剖宮產術孕產婦產后抑郁癥的影響. 中華麻醉學雜志, 2021, 41(3): 274-277.
12.	常俊曉. 艾司氯胺酮復合硬膜外麻醉用于剖宮產術的臨床效果研究. 母嬰世界, 2021, (14): 18,20.
13.	徐敏杰. 艾司氯胺酮在產科緊急剖宮產中的應用研究. 黑龍江醫藥, 2021, 34(4): 879-881.
14.	陶應軍, 曾毅, 彭玲. 微量泵注低劑量艾司氯胺酮對剖宮產產婦產后抑郁的影響觀察. 醫藥前沿, 2021, 11(17): 6-8.
15.	郭杰, 楊春云, 田靜. 小劑量艾司氯胺酮復合舒芬太尼用于剖宮產術后自控靜脈鎮痛的效果. 中國醫藥, 2021, 16(12): 1859-1863.
16.	邢婧, 楊沫, 王希. 艾司氯胺酮在肥胖孕婦剖宮產全麻中的應用研究. 中國計劃生育和婦產科, 2021, 13(11): 69-72.
17.	嚴佳敏, 劉先保. 聯合應用艾司氯胺酮和舒芬太尼的剖宮產術后鎮痛效果及抗抑郁作用. 江蘇醫藥, 2021, 47(11): 1132-1135,1139.
18.	周敏. 艾司氯胺酮在剖宮產術全麻中的應用. 北方藥學, 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. 圍術期非阿片類鎮痛藥的應用進展. 系統醫學, 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.	韋珊珊, 韋寧. 剖宮產術后鎮痛的研究進展. 中國臨床新醫學, 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.	汪蕓薈, 張中軍, 鄭子豪. 右旋氯胺酮的臨床應用研究進展. 今日藥學, 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.	王瑩瑩, 趙璇. 右旋氯胺酮藥理機制和藥物動力學特點及臨床應用的研究進展. 中華實用診斷與治療雜志, 2019, 33(7): 724-728.
33.	李新, 余小玉, 司文鳳. 氯胺酮對新生兒Apgar評分的影響. 河南醫藥信息, 2002, (19): 34-35.
34.	劉絲濛, 岳云. 右氯胺酮的藥理學特點和臨床應用. 國際麻醉學與復蘇雜志, 2016, 37(1): 62-66,71.
35.	余樂, 王清秀. 麻醉藥抗抑郁作用的研究進展. 同濟大學學報(醫學版), 2021, 42(4): 574-580.
36.	趙文莉, 邱妍, 李瑋玲, 等. 一種新機制抗抑郁藥: 艾司氯胺酮. 中國新藥與臨床雜志, 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. 楊帆. 剖宮產術后鎮痛中應用舒芬太尼復合小劑量艾斯氯胺酮的應用效果. 中國保健營養, 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. 劉洋, 李熊剛. 艾司氯胺酮復合氫嗎啡酮對剖宮產術后鎮痛及產后抑郁的影響. 山東醫藥, 2021, 61(19): 84-87.
10. 楊梅, 卞新榮. 艾斯氯胺酮對剖宮產產婦術后鎮痛效果及呼吸循環功能的影響. 齊齊哈爾醫學院學報, 2021, 42(10): 856-859.
11. 顧盼, 姜秀麗, 杜伯祥, 等. 艾司氯胺酮PCIA對剖宮產術孕產婦產后抑郁癥的影響. 中華麻醉學雜志, 2021, 41(3): 274-277.
12. 常俊曉. 艾司氯胺酮復合硬膜外麻醉用于剖宮產術的臨床效果研究. 母嬰世界, 2021, (14): 18,20.
13. 徐敏杰. 艾司氯胺酮在產科緊急剖宮產中的應用研究. 黑龍江醫藥, 2021, 34(4): 879-881.
14. 陶應軍, 曾毅, 彭玲. 微量泵注低劑量艾司氯胺酮對剖宮產產婦產后抑郁的影響觀察. 醫藥前沿, 2021, 11(17): 6-8.
15. 郭杰, 楊春云, 田靜. 小劑量艾司氯胺酮復合舒芬太尼用于剖宮產術后自控靜脈鎮痛的效果. 中國醫藥, 2021, 16(12): 1859-1863.
16. 邢婧, 楊沫, 王希. 艾司氯胺酮在肥胖孕婦剖宮產全麻中的應用研究. 中國計劃生育和婦產科, 2021, 13(11): 69-72.
17. 嚴佳敏, 劉先保. 聯合應用艾司氯胺酮和舒芬太尼的剖宮產術后鎮痛效果及抗抑郁作用. 江蘇醫藥, 2021, 47(11): 1132-1135,1139.
18. 周敏. 艾司氯胺酮在剖宮產術全麻中的應用. 北方藥學, 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. 圍術期非阿片類鎮痛藥的應用進展. 系統醫學, 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. 韋珊珊, 韋寧. 剖宮產術后鎮痛的研究進展. 中國臨床新醫學, 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. 汪蕓薈, 張中軍, 鄭子豪. 右旋氯胺酮的臨床應用研究進展. 今日藥學, 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. 王瑩瑩, 趙璇. 右旋氯胺酮藥理機制和藥物動力學特點及臨床應用的研究進展. 中華實用診斷與治療雜志, 2019, 33(7): 724-728.
33. 李新, 余小玉, 司文鳳. 氯胺酮對新生兒Apgar評分的影響. 河南醫藥信息, 2002, (19): 34-35.
34. 劉絲濛, 岳云. 右氯胺酮的藥理學特點和臨床應用. 國際麻醉學與復蘇雜志, 2016, 37(1): 62-66,71.
35. 余樂, 王清秀. 麻醉藥抗抑郁作用的研究進展. 同濟大學學報(醫學版), 2021, 42(4): 574-580.
36. 趙文莉, 邱妍, 李瑋玲, 等. 一種新機制抗抑郁藥: 艾司氯胺酮. 中國新藥與臨床雜志, 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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