S-ketamine as an adjuvant in patient-controlled intravenous analgesia for preventing postpartum depression: a randomized controlled trial

Yaqian Han, Pule Li, Mengrong Miao, Yuan Tao, Xia Kang, Jiaqiang Zhang, Yaqian Han, Pule Li, Mengrong Miao, Yuan Tao, Xia Kang, Jiaqiang Zhang

Abstract

Background: Postpartum depression (PPD) is a common complication of cesarean section. S-ketamine given intravenously during surgery can help prevent PPD. However, whether S-ketamine in patient-controlled intravenous analgesia (PCIA) can reduce the incidence of PPD is unknown. This study assessed the effect of S-ketamine as an adjuvant in PCIA for preventing PPD in women undergoing cesarean delivery.

Methods: A total of 375 parturients scheduled to undergo cesarean section and then receive PCIA were recruited from a single center and were randomly assigned to control (C) group (sufentanil 2 μg/kg + tropisetron 10 mg) or S-ketamine (S) group (S-ketamine 0.5 mg/kg + sufentanil 2 μg/kg + tropisetron 10 mg). The primary outcome was the incidence of PPD measured by the Edinburgh postnatal depression scale (EPDS) after surgery. The secondary outcomes were EPDS scores, visual analog scale (VAS) scores, Ramsay sedation scale (RSS) scores, and the rate of adverse events, including headache, nausea, dizziness, drowsiness, and vomit.

Results: A total of 275 puerperal women were included in the study. The rate of depression in parturient on postoperative days 3, 14, 28 in the C group and S group were 17.6 and 8.2% (p < 0.05), 24.2 and 9.8% (p < 0.05), and 19.0 and 17.2% (p = 0.76) respectively. EPDS scores in the C group and S group on postoperative days 3,14, and 28 were 7.65 ± 3.14 and 6.00 ± 2.47 (p < 0.05), 7.62 ± 3.14 and 6.38 ± 2.67 (p < 0.05), and 7.35 ± 3.17 and 6.90 ± 2.78 (p = 0.15), respectively. The rate of adverse events in the C group and S group were headache 3.3 and 4.1% (p = 0.755), nausea 5.9 and 8.2% (p = 0.481), dizziness 9.2 and 12.3% (p = 0.434), drowsiness 6.5 and 10.7%(p = 0.274), and vomit 5.9 and 5.7% (p = 0.585).

Conclusions: S-ketamine (0.01 mg/kg/h) as an adjuvant in PCIA significantly reduces the incidence of PPD within 14 days and relieves pain within 48 h after cesarean delivery, without increasing the rate of adverse reactions.

Trial registration: Registered in the Chinese Clinical Trial Registry ( ChiCTR2100050263 ) on August 24, 2021.

Keywords: Cesarean section; PCIA; Patient-controlled intravenous analgesia; Postpartum depression; Puerperal women; S-ketamine.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of patient selection
Fig. 2
Fig. 2
Rate of postpartum depression (PPD) after cesarean delivery. *P < 0.05
Fig. 3
Fig. 3
Edinburgh postnatal depression scale (EPDS) scores at different time points. *P 

Fig. 4

Visual analog scale (4a) and…

Fig. 4

Visual analog scale (4a) and Ramsay sedation scale (4b) scores at different time…

Fig. 4
Visual analog scale (4a) and Ramsay sedation scale (4b) scores at different time points after cesarean delivery. **P 
Similar articles
Cited by
References
    1. Alipoor M, Loripoor M, Kazemi M, Farahbakhsh F, Sarkoohi A. The effect of ketamine on preventing postpartum depression. J Med Life. 2021;14(1):87–92. doi: 10.25122/jml-2020-0116. - DOI - PMC - PubMed
    1. Yamamoto N, Abe Y, Arima K, Nishimura T, Akahoshi E, Oishi K, et al. Mental health problems and influencing factors in Japanese women 4 months after delivery. J Physiol Anthropol. 2014;33(1):32. doi: 10.1186/1880-6805-33-32. - DOI - PMC - PubMed
    1. Xu Y, Li Y, Huang X, Chen D, She B, Ma D. Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective clinical trial. Arch Gynecol Obstet. 2017;295(5):1167–1174. doi: 10.1007/s00404-017-4334-8. - DOI - PubMed
    1. Morris LS, Costi S, Tan A, Stern ER, Charney DS, Murrough JW. Ketamine normalizes subgenual cingulate cortex hyper-activity in depression. Neuropsychopharmacology. 2020;45(6):975–981. doi: 10.1038/s41386-019-0591-5. - DOI - PMC - PubMed
    1. Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet. 2014;384(9956):1789–1799. doi: 10.1016/s0140-6736(14)61278-2. - DOI - PubMed
Show all 29 references
Publication types
MeSH terms
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Fig. 4
Fig. 4
Visual analog scale (4a) and Ramsay sedation scale (4b) scores at different time points after cesarean delivery. **P 

References

    1. Alipoor M, Loripoor M, Kazemi M, Farahbakhsh F, Sarkoohi A. The effect of ketamine on preventing postpartum depression. J Med Life. 2021;14(1):87–92. doi: 10.25122/jml-2020-0116.
    1. Yamamoto N, Abe Y, Arima K, Nishimura T, Akahoshi E, Oishi K, et al. Mental health problems and influencing factors in Japanese women 4 months after delivery. J Physiol Anthropol. 2014;33(1):32. doi: 10.1186/1880-6805-33-32.
    1. Xu Y, Li Y, Huang X, Chen D, She B, Ma D. Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective clinical trial. Arch Gynecol Obstet. 2017;295(5):1167–1174. doi: 10.1007/s00404-017-4334-8.
    1. Morris LS, Costi S, Tan A, Stern ER, Charney DS, Murrough JW. Ketamine normalizes subgenual cingulate cortex hyper-activity in depression. Neuropsychopharmacology. 2020;45(6):975–981. doi: 10.1038/s41386-019-0591-5.
    1. Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet. 2014;384(9956):1789–1799. doi: 10.1016/s0140-6736(14)61278-2.
    1. Zhan Y, Zhang B, Zhou Y, Zheng W, Liu W, Wang C, et al. A preliminary study of anti-suicidal efficacy of repeated ketamine infusions in depression with suicidal ideation. J Affect Disord. 2019;251:205–212. doi: 10.1016/j.jad.2019.03.071.
    1. Reinert J, Parmentier BL. Effect of perioperative ketamine on postoperative mood and depression: a review of the literature. Expert Rev Clin Pharmacol. 2021;14(1):25–32. doi: 10.1080/17512433.2021.1855142.
    1. Yao J, Song T, Zhang Y, Guo N, Zhao P. Intraoperative ketamine for reduction in postpartum depressive symptoms after cesarean delivery: a double-blind, randomized clinical trial. Brain Behav. 2020;10(9):e01715. doi: 10.1002/brb3.1715.
    1. Zanos P, Moaddel R, Morris P, Riggs L, Highland J, Georgiou P, et al. Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacol Rev. 2018;70(3):621–660. doi: 10.1124/pr.117.015198.
    1. Sinner B, Graf B. Ketamine. Handb Exp Pharmacol. 2008;182:313–333. doi: 10.1007/978-3-540-74806-9_15.
    1. Wang J, Huang J, Yang S, Cui C, Ye L, Wang SY, et al. Pharmacokinetics and safety of Esketamine in Chinese Parturients undergoing painless gastroscopy in comparison with ketamine: a randomized, open-label clinical study. Drug Des Devel Ther. 2019;13:4135–4144. doi: 10.2147/dddt.S224553.
    1. Krystal JH, Charney DS, Duman RS. A new rapid-acting antidepressant. Cell. 2020;181(1):7. doi: 10.1016/j.cell.2020.02.033.
    1. Hashimoto K. Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochem Pharmacol. 2020;177:113935. doi: 10.1016/j.bcp.2020.113935.
    1. Zou L, Tian SY, Quan X, Ye TH. Psychedelic effects of subanesthetic doses of ketamine. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2009;31(1):68–72.
    1. Gaudet C, Wen SW, Walker MC. Chronic perinatal pain as a risk factor for postpartum depression symptoms in Canadian women. Can J Public Health. 2013;104(5):e375–e387. doi: 10.17269/cjph.104.4029.
    1. Ma JH, Wang SY, Yu HY, Li DY, Luo SC, Zheng SS, et al. Prophylactic use of ketamine reduces postpartum depression in Chinese women undergoing cesarean section. Psychiatry Res. 2019;279:252–258. doi: 10.1016/j.psychres.2019.03.026.
    1. Lascelles K, Marzano L, Brand F, Trueman H, McShane R, Hawton K. Effects of ketamine treatment on suicidal ideation: a qualitative study of parturients' accounts following treatment for depression in a UK ketamine clinic. BMJ Open. 2019;9(8):e029108. doi: 10.1136/bmjopen-2019-029108.
    1. Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data Meta-analysis. Am J Psychiatry. 2018;175(2):150–158. doi: 10.1176/appi.ajp.2017.17040472.
    1. Hinkle SN, Buck Louis GM, Rawal S, Zhu Y, Albert PS, Zhang C. A longitudinal study of depression and gestational diabetes in pregnancy and the postpartum period. Diabetologia. 2016;59(12):2594–2602. doi: 10.1007/s00125-016-4086-1.
    1. Chen Y, Ye X, Wu H, Huang X, Ke C, Chen Y, et al. Association of Postpartum Pain Sensitivity and Postpartum Depression: a prospective observational study. Pain Ther. 2021. 10.1007/s40122-021-00325-1.
    1. Costafreda SG, Chu C, Ashburner J, Fu CH. Prognostic and diagnostic potential of the structural neuroanatomy of depression. PLoS One. 2009;4(7):e6353. doi: 10.1371/journal.pone.0006353.
    1. Meltzer-Brody S, Boschloo L, Jones I, Sullivan PF, Penninx BW. The EPDS-lifetime: assessment of lifetime prevalence and risk factors for perinatal depression in a large cohort of depressed women. Arch Womens Ment Health. 2013;16(6):465–473. doi: 10.1007/s00737-013-0372-9.
    1. Grace SL, Evindar A, Stewart DE. The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature. Arch Womens Ment Health. 2003;6(4):263–274. doi: 10.1007/s00737-003-0024-6.
    1. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh postnatal depression scale. Br J Psychiatry. 1987;150:782–786. doi: 10.1192/bjp.150.6.782.
    1. Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134–1142. doi: 10.1176/appi.ajp.2013.13030392.
    1. Singh JB, Fedgchin M, Daly E, Xi L, Melman C, De Bruecker G, et al. Intravenous Esketamine in adult treatment-resistant depression: a double-blind, double-randomization. Placebo-Controlled Study. Biol Psychiatry. 2016;80(6):424–431. doi: 10.1016/j.biopsych.2015.10.018.
    1. Lei Y, Liu H, Xia F, Gan S, Wang Y, Huo W, et al. Effects of Esketamine on acute and chronic pain after Thoracoscopy pulmonary surgery under general anesthesia: a multicenter-prospective, randomized, double-blind, and controlled trial. Front Med (Lausanne) 2021;8:693594. doi: 10.3389/fmed.2021.693594.
    1. Salloum NC, Fava M, Hock RS, Freeman MP, Flynn M, Hoeppner B, et al. Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression. J Affect Disord. 2020;260:131–139. doi: 10.1016/j.jad.2019.09.017.
    1. Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000;157(6):924–930. doi: 10.1176/appi.ajp.157.6.924.

Source: PubMed

3
Subscribe