{"paper_id":"4167c7c0-97fd-41d8-8b4f-b408dd00d372","body_text":"Effect of Single Intravenous Injection of Esketamine on Postpartum Depression after Labor Analgesia and Potential Mechanisms: A Randomized, Double-blinded Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of Single Intravenous Injection of Esketamine on Postpartum Depression after Labor Analgesia and Potential Mechanisms: A Randomized, Double-blinded Controlled Trial Bin Ling, Yun Zhu, Zelin Yan, Hao Chen, Hua Xu, Qi Wang, Wanyou Yu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3100226/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Nov, 2023 Read the published version in BMC Pharmacology and Toxicology → Version 1 posted 4 You are reading this latest preprint version Abstract Background： The study was designed to investigate effects of single intravenous injection of esketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms. Methods： A total of 120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 hours, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05. Results： The incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs 15.3%, p = 0.004 and 5.2% vs 18.6%, p = 0.006, respectively) . There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 hours after delivery were similar between the two groups. Conclusions： Single intravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation. Esketamine Depression Postpartum Analgesia Obstetrical Figures Figure 1 Introduction Due to the particularity of physiology, maternal perinatal safety has been a special concern. At present, the rate of cesarean section in China has exceeded 15% set by the World Health Organization. Therefore, in order to reduce the rate of cesarean section and build a modern civilized obstetrics department with humanistic care, the labor analgesia is gradually recommended on the premise of ensuring maternal and fetal safety [1]. Postpartum depression (PPD) is a mental illness occurring in the puerperium, showing a series symptoms such as depression, sadness, crying, irritability, even hallucinations or suicide, which seriously endangers the physical and mental health of pregnant women[2, 3]. PPD is related to maternal psychological and physical, family, social and obstetric factors, and occurs during six weeks after delivery in either primigravida or multipara undergoing cesarean section or vaginal delivery[4, 5], with the incidence even up to 38.5% [6]. Due to its high incidence and harmfulness, the treatment and prevention of PPD have become an important topic. Nowadays, medication combined with psychological counseling are mainly used for the treatment of PPD. However, long-term medication may have side effects for lactating women on the infant's motional, behavioral and neurological development [7]. Thus, prevention of PPD is even more important than treatment. As an intravenous anesthetic drug, ketamine is often used in pediatric, obstetric, and outpatient anesthesia. In addition, as a psychotropic drug, the antidepressant effect of ketamine is also gradually recognized. Studies have shown that ketamine can significantly reduce the incidence and severity of depression [8, 9]. As an isomer of ketamine, compared with racemic ketamine, esketamine has stronger analgesic and sedative effects, smaller cardiovascular and psychiatric adverse effects, and can also be used in patients with refractory, severe depression and epilepsy [10]. Our previous studies have suggested that esketamine prevent PPD in women underwent cesarean section [11, 12]. However, with the widespread use of labor analgesia in obstetrics, it was also unknown whether esketamine was effective in such maternal postpartum depression. Additionally, the mechanisms of antidepressant effects of esketamine were unclear now. Therefore, we designed the study which was aimed to confirm the antidepressant effect of esketamine in women underwent labor analgesia and explore potential mechanisms. Methods Study design This randomized, double-blinded, controlled trial was conducted at the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China, from 6/1/2022 to 2/28/2023, which performed in accordance with the declaration of Helsinki. The study protocol was approved by the medical ethics committee of our hospital on 1/14/2022 (Ethical approval number: 2021-03-031-K01). Then, the study was registered at the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number—ChiCTR2200060387). All participants signed the informed consent form before enrollment. Study participants One hundred and twenty primiparous women who underwent labor analgesia, aged 22 to 38, with American society of Aneshesiologists (ASA) physical status II, were enrolled. The exclusion criteria were as follows: not suitable for transvaginal delivery; combined with coagulation disorders; having mental disorder; organic or pharmacogenic depression before delivery; failure of epidural puncture; changed to cesarean section. Sample size estimation Based on the results of our pre-experiment (10 participants in each group), the incidence of PPD at 6 weeks after delivery can be reduced by 12% in the tested group. Power analysis showed that a reduction rate of 15% with α = 0.05 and a 10% dropout rate within a power value of 90%, a sample size of at least 54 per group were needed. A total of 120 samples were designed in this study, for 60 in each group respectively. Figure 1 showed the consolidated standards of reporting trials (CONSORT) flow diagram of the study participant’s recruitment. Randomization and allocation concealment Participants were randomly assigned to one of two groups. Random tables were generated by SPSS 20.0. One hundred and twenty sealed envelopes were prepared by a statistician who did not participate in the study. The study was performed with neither patients’ nor observers’ awareness of the group to which each patient belonged. To assure concealment of allocation, numbers were kept in sealed and opaque envelopes, which were opened by an anaesthesiologist who was not involved in the study. Study interventions After entering the delivery room, peripheral venous access was opened in all participants, maternal heart rate, noninvasive blood pressure measurement, electrocardiography and pulse oximetry were monitored. All women were received oxygen for 3 L/min by transnasal catheter. Epidural anaesthesia were operated between L 2 and L 3 after cervical dilation up to 2 ~ 3 cm. After successful puncture, the epidural catheter was placed for 3.5 cm toward the head position and 1% lidocaine was injected for 3 ml. The epidural analgesia pump was connected, in which was 0.75% ropivacaine hydrochloride (20 ml) were diluted by normal saline up to 100 ml. All pumps were set with a bolus of 10 ml, continuous infusion amount of 8 ml/h, single dose of 4 ml, locking time of 15 min and stopped after fetal disengagement. Esketamine (0.2 mg/kg) was intravenously injected after fetal disengagement in the test group (Group E), while the placebo (normal saline) was administered in the control group (Group C). Labor analgesia was performed by the same anesthesiologist and esketamine or placebo were administrated by the same nurse anesthetist. Perinatal management was completed by the same obstetric team. Neither the subjects and the investigators were aware of the enrollment. Outcome measurements The primary outcomes of the study were the incidence of PPD at one week and six weeks after delivery. The diagnosis of postpartum depression was based on the reference [13] and [14], in which the depression score (Edinburgh Postpartum Depression Scale, EPDS) and the diagnostic criteria for mental disorders are included. Ramsay sedation score before analgesia (T 0 ), 5 (T 1 ), 10 (T 2 ), 20 (T 3 ), 30 (T 4 ) and 60 (T 5 ) minutes after administration of esketamine were measured. The scoring criteria [15] were as follows: 1 point, patients were awake, feeling anxiety or irritability; 2 points, patients were awake, being cooperative, directional or quiet; 3 points, patients were awake, only being responsive to commands; 4 points, patients were asleep, being responsive quickly to tapping eyebrow or soft tone stimulation; 5 points, patients were asleep, being responsive slowly to tapping eyebrow or strong acoustic stimulation; 6 points, patients were asleep, being no responsive to tapping eyebrow or strong acoustic stimulation. All women were tested levels of norepinephrine (NE), epinephrine (E) ,C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-10 (IL-10) in peripheral venous blood before labor analgesia (when the woman was quiet in the ward), at 24 hours, 1 week, and 6 weeks after delivery. Serum concentrations of IL-6 and IL-10 were determined by enzyme linked immunosorbent assay (ELISA). The volume of postpartum hemorrhage was calculated for 24 hours after delivery. Side effects such as nightmares, drowsiness, nausea and vomiting were measured for 48 hours after delivery as well. Statistical analysis The statistical analysis were performed using SPSS software package (version 25.0; IBM, Inc., Chicago, IL, USA). The continuous data were presented as mean (M) ± standard deviation (SD) and examined by independent t-test. The categorical data were shown as n(%) and examined with a Chi-square test. It was considered statistically significant since a p value < 0.05. Results Patient recruitment In the study, a total of 120 participants were enrolled initially and three participants were excluded during the trial. One case was excluded for failure of epidural puncture, and another one was for changed to cesarean section in Group E, while one participant was excluded for failure of epidural puncture in Group C. Finally, There were 117 participants included in the statistical analysis (58 in Group E and 59 in Group C, respectively. Figure 1 , CONSORT flow diagram). Patient characteristics There were no significant difference of the patient characteristics (age, heigh, weight, BMI, gestational week, volume of postpartum hemorrhage) between the two groups (Table 1 ). Table 1 Baseline characteristics of the studied groups Characteristic Group E (n = 58) Group C (n = 59) P- value a Age (years) 28.2 ± 4.8 27.8 ± 4.4 0.656 Gestational age (weeks) 38.8 ± 3.7 39.0 ± 2.6 0.338 Height (cm) 159.2 ± 6.7 157.8 ± 6.2 0.419 Weight (kg) 67.8 ± 7.1 66.9 ± 5.9 0.813 BMI (kg/m 2) 28.2 ± 4.1 27.8 ± 3.6 0.249 Postpartum hemorrhage (ml) 216.5 ± 33.8 202.3 ± 39.2 0.825 Data presented as mean ± Standard Deviation BMI: Body mass index a Independent sample t-test Ramsay sedation score There were no significant difference of the Ramsay sedation score at T 0 and T 5 between the two groups. Compared with Group C, the Ramsay sedation score at T 1 , T 2 , T 3 and T 4 were significantly higher in Group E (Table 2 ). Table 2 Ramsay sedation score in the two groups Group T 0 T 1 T 2 T 3 T 4 T 5 Group E (n = 58) 1.65 ± 0.38 2.48 ± 0.45 2.57 ± 0.51 2.64 ± 0.49 2.58 ± 0.52 1.72 ± 0.43 Group C (n = 59) 1.71 ± 0.44 1.85 ± 0.41 2.07 ± 0.43 2.12 ± 0.38 2.08 ± 0.42 1.75 ± 0.40 P- value a 0.218 0.001 0.003 0.006 0.005 0.556 Data presented as mean ± Standard Deviation a Independent sample t-test Incidence of PPD and side effects The incidence of PPD was significantly decreased both for one week and six weeks after delivery in Group E (3.4% vs 15.3%, p = 0.004 and 5.2% vs 18.6%, p = 0.006, respectively).The incidence of side effects after delivery were similar between the two groups (Table 3 ). Table 3 Occurrence of PPD and side effects in the two groups Group PPD nausea, vomiting drowsiness nightmares 1 week 6 weeks Group E (n = 58) 2(3.4) 3(5.2) 2(3.4) 1(1.7) 2(3.4) Group C (n = 59) 9(15.3) 11(18.6) 1(1.7) 1(1.7) 3(5.1) P- value a 0.004 0.006 0.695 0.784 0.815 Data presented as number (percentage) PPD: postpartum depression a Chi square Levels of NE, E, CRP, IL-6 and IL-10 There were no significant difference of the levels of NE, E, CRP, IL-6 and IL-10 between the two groups before labor analgesia and 6 weeks after delivery. Compared with Group C, the levels of NE, E, CRP and IL-6 were significantly lower for 24 hours and 1 week after delivery in Group E, while IL-10 were higher at the same time (Table 4 ). Table 4 Levels of NE, E CRP, IL-6 and IL-10 in the two groups Variables Group Before analgesia 24 h after delivering 1st week after delivering 6th week after delivering NE (nmol/L) Group E (n = 58) 4.36 ± 0.77 3.11 ± 0.54 2.95 ± 0.49 3.06 ± 0.54 Group C (n = 59) 4.58 ± 0.84 4.24 ± 0.71 4.15 ± 0.73 3.31 ± 0.61 p value 0.629* 0.009* 0.004* 0.428* E (pmol/L) Group E (n = 58) 526.3 ± 38.6 367.2 ± 29.1 339.4 ± 24.7 326.5 ± 23.3 Group C (n = 59) 549.8 ± 44.5 481.7 ± 37.4 477.9 ± 33.6 341.1 ± 28.6 P- value a 0.858 0.001 0.006 0.359 CRP (mg/L) Group E (n = 58) 2.52 ± 0.69 7.87 ± 1.38 6.35 ± 1.12 2.84 ± 0.81 Group C (n = 59) 2.47 ± 0.75 10.98 ± 1.76 8.27 ± 1.33 3.02 ± 0.94 P- value a 0.228 0.008 0.005 0.656 IL−6 (ng/L) Group E (n = 58) 78.8 ± 9.6 145.6 ± 12.1 108.4 ± 11.2 81.5 ± 8.7 Group C (n = 59) 76.9 ± 8.7 186.2 ± 15.6 141.3 ± 12.6 79.8 ± 9.1 P- value a 0.326 0.007 0.002 0.526 IL−10 (µg/L) Group E (n = 58) 15.2 ± 5.3 8.7 ± 3.4 10.7 ± 5.2 13.9 ± 6.1 Group C (n = 59) 16.7 ± 6.5 5.1 ± 2.2 6.9 ± 3.1 15.1 ± 6.7 P- value a 0.916 0.004 0.005 0.778 Data presented as mean ± Standard Deviation NE: norepinephrine; E: epinephrine; CRP: C-reactive protein; IL-6: interleukin-6; IL-10: interleukin-10 a Independent sample t-test In the study, a total of 120 participants were enrolled initially and three participants were excluded during the trial. Finally, There were 117 participants included in the statistical analysis (58 in Group E and 59 in Group C, respectively). CONSORT: the Consolidated Standards of Reporting Trials. Discussion Pain in the perinatal period is one of the factors leading to the development of PPD. The symptoms of PPD are more prominent in women who experience frequent pain during childbirth [16]. Although maternal pain can be relieved by labor analgesia, psychological degeneration, emotional vulnerability, stress response and inflammation may also lead to a high occurrence of PPD [17]. The results of this study showed that single intravenous injection of esketamine decreased the occurrence of PPD for one week and six weeks after delivery in women underwent labor analgesia without increasing related side effects. The traditional treatment for depression is to increase the amount of serotonin in the synaptic space to achieve the effect of alleviating depression, but these antidepressants are slow to act, generally taking three to six weeks to achieve therapeutic effects [18]. In 2019, the U. S. Food and Drug Administration (FDA) granted esketamine for the treatment of major depressive disorder and drug-resistant depression with urgent suicide risk. The results of a meta-analysis indicated that esketamine can significantly improve the patients' low mood, low self-evaluation, and even weaken the suicidal ideation, especially improve the therapeutic effect for treatment resistant depression (TRD) [19]. Another retrospective analysis have showed that both esketamine's approval for use in TRD and longer-term safety data may position it preferentially above racemic ketamine, though the efficacy of esketamine compared to racemic ketamine remained unclear [20]. However, there are few studies on esketamine used in postpartum depression. Our previous studies indicated that the incidence of PPD was reduced by prophylactic intravenous use of esketamine or combined with patient control intravenous analgesia for women underwent cesarean section [11, 12]. The study of Wang et al [21] also have showed that the application of esketamine after cesarean section can effectively reduce depression-related scores and the risk of postpartum depression without increasing adverse reactions and had high safety. However, a lower dose of esketamine was used in our study. Based on previous studies, we applied esketamine to the prevention of postpartum depression in labor analgesia and achieved certain results in this study. As endocrine hormones, NE and E can affect the the bodys’ mood by modulating the sensitivity of neuronal synapses and neurotransmitters [22]. NE can return to the synaptic space under the action of NE transporter protein, and also form E by acting on phenylmethylamine-N-methyltransferase, which easily lead to fear and tension [23]. It had been reported that the blue spot located in the brain stem was activated due to the changes in stress and hormone levels during pregnancy, thus releasing a large number of NE to participate in the regulation of the nervous system, which was easy to cause tension and depression [24]. In this study, the levels of NE and E were significantly lower at 24 hours and 1 week after delivery in Group E than in Group C, which also suggested that the maternal stress response was decreased in the tested group. The antidepressant mechanism may be the target of esketamine for monoaminergic nervous system, can affect the brain stem blue spot, and further affect the noradrenergic system, promote the transcription and expression of the gene, increase the synthesis of transporter, resulting in NE migration from plasma membrane to cytoplasm, decrease the concentration of serum NE and E [25]. Additionally, due to the sedative and analgesic effects of esketamine, the Ramsay sedation score was decreased at 5, 10, 20 and 30 minutes after administration of esketamine in this study, which might be one of the reasons for the reduced stress response in the tested group. As a non-specific inflammatory marker, CRP reflects the stress and inflammation response of the human body. When infection and injury take palce, CRP rises sharply in the plasma [26]. Besides, among the inflammatory mediators released by the human body under pain and traumatic stress, IL-6 is the earliest and highly sensitive proinflammatory factor expressed, which is closely related to the size of trauma, body immune status and prognosis [27]. IL-10 is an inflammatory suppressor, which can exert an anti-inflammatory effect by inhibiting nuclear factors activity and promoting neutrophil apoptosis to reduce pro-inflammatory factors [28]. Therefore, the levels of CRP, IL-6 and IL-10 were observed in the present study to measure the effects of esketamine on inflammatory response. In this study, the levels of CRP and IL-6 were significantly lower at 24 hours and 1 week after delivery in the tested group, while IL-10 were higher at the same time. This results indicated that the antidepressant effect of esketamine might be related to the reduced inflammatory response in puerperants underwent labor analgesia. Studies have shown the brain causes negative emotions by the clustering of the lateral halterate nucleus, where the excitatory transmitter is the N-methyl-D-aspartate (NMDA) receptor of the glutamate-gated ion channel[29, 30]. As a blocker of the glutamate-gated ion channel NMDA receptor, the main antidepressant mechanism of esketamine is to sustainable block the NMDA receptor, block the elongation factor 2 (eEF 2) kinase, increase the release of brain-derived neurotrophic factor (BDNF) and the expression of tropomyosin receptor kinase B (TrkB), induce rapamycin target complex 1 (mTORC1) signaling pathway and extracellular regulatory protein kinase (ERK) activation, improve neuroplasticity and synapse formation [31, 32]. In short, the traditional treatment of antidepression drugs is to stimulate the “reward center\" of the brain, while esketamine is to remove the inhibitory effect of the \"reward center”. Esketamine has been used clinically for many years as an anesthetic drug, but the evidence is still insufficient as an antidepressant drug. Considering the possible side effects such as nightmare, hallucination and abusement, esketamine was used only once in the study and was lower than the subanesthetic dose. In addition, through the follow-up after delivery, we found that the adverse reactions did not increase in the test group. There were some limitations in this study, such as the strong subjectivity of the PPD evaluation by EPDS. To minimize the subjective differences, the PPD valuator in this study was the same physician who did not participate in the specific study. Furthermore, the objective indicators such as levels of, NE, E, CRP, IL−6 and IL−10 were also combined in the study, which could better reflect maternal depression. Furthermore, the severity of PPD was not measured in this study, which would be content of next studies. Conclusions In conclusion, single intravenous injection of esketamine (0.2 mg/kg) after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation. Declarations Authors’ contributions BL, YZ, HX and WW designed the study. QWsupervised the practical carrying out of the clinical trial. WY participated in the study’s conceptualization and sampling. ZY and HX analyzed the data. BL, YZ and WW wrote the manuscript. All authors read and approved the final manuscript. Funding No funding was received for conducting this study. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Wei Wang, e-mail: [email protected] . Ethics approval and consent to participate The study was performed in accordance with the declaration of Helsinki. Ethical approval for this study (2021-03-031-K01) was provided by the Institutional Ethics Committee of the Affiliated Jiangning Hospital of Nanjing Medical University. The registration of this study was approved in the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number—ChiCTR2200060387). All volunteers involved were informed of the proposal and gave their written, informed consent. Consent for publication Not Applicable. Competing interests The authors declare no conflict of interests. Abbreviations PPD postpartum depression ASA American society of Aneshesiologists CONSORT consolidated standards of reporting trials EPDS Edinburgh Postpartum Depression Scale NE norepinephrine E epinephrine CRP C-reactive protein IL-6 interleukin-6 IL-10 interleukin-10 NMDA N-methyl-D-aspartate References Zhao P, Cai Z, Huang A, Liu C, Li H, Yang S, Hu LQ. 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Rethinking ketamine and esketamine action: Are they antidepressants with mood-stabilizing properties? Eur Neuropsychopharmacol. 2023; 70:49-55. Liu B, Du Y, Xu C, Liu Q, Zhang L. Antidepressant effects of repeated s-ketamine administration as NMDAR Antagonist: Involvement of CaMKIIα and mTOR signaling in the hippocampus of CUMS mice. Brain Res. 2023; 1811:148375. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Nov, 2023 Read the published version in BMC Pharmacology and Toxicology → Version 1 posted Editorial decision: Major revision 04 Aug, 2023 Editor assigned by journal 02 Aug, 2023 Submission checks completed at journal 28 Jun, 2023 First submitted to journal 23 Jun, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-3100226\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":213921644,\"identity\":\"90f8bc02-04aa-49b5-b8b5-01939a7f84b5\",\"order_by\":0,\"name\":\"Bin Ling\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the Affiliated Jiangning Hospital of Nanjing Medical University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Bin\",\"middleName\":\"\",\"lastName\":\"Ling\",\"suffix\":\"\"},{\"id\":213921645,\"identity\":\"984b360d-2e09-4458-bece-7fcaf8f6df7a\",\"order_by\":1,\"name\":\"Yun Zhu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Nanjing Jiangning Hospital of Traditional Chinese Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yun\",\"middleName\":\"\",\"lastName\":\"Zhu\",\"suffix\":\"\"},{\"id\":213921647,\"identity\":\"b8389ad9-553e-4a90-a295-5659c21e6673\",\"order_by\":2,\"name\":\"Zelin Yan\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the Affiliated Jiangning Hospital of Nanjing Medical University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zelin\",\"middleName\":\"\",\"lastName\":\"Yan\",\"suffix\":\"\"},{\"id\":213921650,\"identity\":\"63f4505b-d154-4d73-8b42-74806a1fd1a1\",\"order_by\":3,\"name\":\"Hao Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the Affiliated Jiangning Hospital of Nanjing Medical University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hao\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":213921652,\"identity\":\"3e13a3aa-98bf-4efb-b74a-bd1adc5ef59b\",\"order_by\":4,\"name\":\"Hua Xu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the Affiliated Jiangning Hospital of Nanjing Medical University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hua\",\"middleName\":\"\",\"lastName\":\"Xu\",\"suffix\":\"\"},{\"id\":213921654,\"identity\":\"563ad6d2-1efb-4d8e-ab3b-08f33766c8bc\",\"order_by\":5,\"name\":\"Qi Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the Affiliated Jiangning Hospital of Nanjing Medical University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Qi\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":213921655,\"identity\":\"0a84a2b6-0cee-4d89-8ef8-7d11d9f5fcb5\",\"order_by\":6,\"name\":\"Wanyou Yu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the Affiliated Jiangning Hospital of Nanjing Medical University\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Wanyou\",\"middleName\":\"\",\"lastName\":\"Yu\",\"suffix\":\"\"},{\"id\":213921657,\"identity\":\"ac11bda3-4af7-4149-8d8d-9dadc85750b7\",\"order_by\":7,\"name\":\"Wei Wang\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYPACCTk29obEBwkVNcRrMebnOfDY4MGZY8RbkzhzRuIzyYctzISVGhw/e/g1T4UF44YDyWkViQ1sDPzt3Qn4tZzJS7PmOSPBbHDgWNqNxB0yDBJnzm7Aq8XsQI6ZcW6bBJvBwR6gljNsDAYSuQS0nH8D1PJPgsfgMP+3gsQ2ZiK03MgxfpzbICEh2caQxkCUFvsbb8yY/xyTMODnYUiWSDhzjIegXyT7c4w/zqipq2+Tf5D48UdFjRx/ey9+LUDAJoHM4yGkHASYPxCjahSMglEwCkYwAAAfhkxTtTyHZwAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"the Affiliated Jiangning Hospital of Nanjing Medical University\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Wei\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2023-06-23 11:59:27\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-3100226/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-3100226/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s40360-023-00705-7\",\"type\":\"published\",\"date\":\"2023-11-23T15:01:39+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":39387310,\"identity\":\"f5718b4f-72f1-47b6-94ed-acafc2a8ec44\",\"added_by\":\"auto\",\"created_at\":\"2023-06-30 18:12:16\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":126002,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eCONSORT flow diagram\\u003c/p\\u003e\\n\\u003cp\\u003eIn the study, a total of 120 participants were enrolled initially and three participants were excluded during the trial. Finally, There were 117 participants included in the statistical analysis (58 in Group E and 59 in Group C, respectively). CONSORT: the Consolidated Standards of Reporting Trials.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3100226/v1/20f75ab3f036c8bcc1459dfb.jpg\"},{\"id\":47146388,\"identity\":\"e8e72933-1e19-474b-9503-fbfbb67b8273\",\"added_by\":\"auto\",\"created_at\":\"2023-11-27 15:07:49\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":501019,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3100226/v1/eec4f784-4ac0-4a07-8ba8-a390ee7ee612.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Effect of Single Intravenous Injection of Esketamine on Postpartum Depression after Labor Analgesia and Potential Mechanisms: A Randomized, Double-blinded Controlled Trial\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eDue to the particularity of physiology, maternal perinatal safety has been a special concern. At present, the rate of cesarean section in China has exceeded 15% set by the World Health Organization. Therefore, in order to reduce the rate of cesarean section and build a modern civilized obstetrics department with humanistic care, the labor analgesia is gradually recommended on the premise of ensuring maternal and fetal safety [1]. Postpartum depression (PPD) is a mental illness occurring in the puerperium, showing a series symptoms such as depression, sadness, crying, irritability, even hallucinations or suicide, which seriously endangers the physical and mental health of pregnant women[2, 3]. PPD is related to maternal psychological and physical, family, social and obstetric factors, and occurs during six weeks after delivery in either primigravida or multipara undergoing cesarean section or vaginal delivery[4, 5], with the incidence even up to 38.5% [6]. Due to its high incidence and harmfulness, the treatment and prevention of PPD have become an important topic.\\u003c/p\\u003e \\u003cp\\u003eNowadays, medication combined with psychological counseling are mainly used for the treatment of PPD. However, long-term medication may have side effects for lactating women on the infant's motional, behavioral and neurological development [7]. Thus, prevention of PPD is even more important than treatment. As an intravenous anesthetic drug, ketamine is often used in pediatric, obstetric, and outpatient anesthesia. In addition, as a psychotropic drug, the antidepressant effect of ketamine is also gradually recognized. Studies have shown that ketamine can significantly reduce the incidence and severity of depression [8, 9]. As an isomer of ketamine, compared with racemic ketamine, esketamine has stronger analgesic and sedative effects, smaller cardiovascular and psychiatric adverse effects, and can also be used in patients with refractory, severe depression and epilepsy [10]. Our previous studies have suggested that esketamine prevent PPD in women underwent cesarean section [11, 12]. However, with the widespread use of labor analgesia in obstetrics, it was also unknown whether esketamine was effective in such maternal postpartum depression. Additionally, the mechanisms of antidepressant effects of esketamine were unclear now. Therefore, we designed the study which was aimed to confirm the antidepressant effect of esketamine in women underwent labor analgesia and explore potential mechanisms.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy design\\u003c/h2\\u003e \\u003cp\\u003e This randomized, double-blinded, controlled trial was conducted at the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China, from 6/1/2022 to 2/28/2023, which performed in accordance with the declaration of Helsinki. The study protocol was approved by the medical ethics committee of our hospital on 1/14/2022 (Ethical approval number: 2021-03-031-K01). Then, the study was registered at the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number\\u0026mdash;ChiCTR2200060387). All participants signed the informed consent form before enrollment.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy participants\\u003c/h2\\u003e \\u003cp\\u003eOne hundred and twenty primiparous women who underwent labor analgesia, aged 22 to 38, with American society of Aneshesiologists (ASA) physical status II, were enrolled. The exclusion criteria were as follows: not suitable for transvaginal delivery; combined with coagulation disorders; having mental disorder; organic or pharmacogenic depression before delivery; failure of epidural puncture; changed to cesarean section.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eSample size estimation\\u003c/h2\\u003e \\u003cp\\u003eBased on the results of our pre-experiment (10 participants in each group), the incidence of PPD at 6 weeks after delivery can be reduced by 12% in the tested group. Power analysis showed that a reduction rate of 15% with \\u003cem\\u003eα\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.05 and a 10% dropout rate within a power value of 90%, a sample size of at least 54 per group were needed. A total of 120 samples were designed in this study, for 60 in each group respectively. Figure\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e showed the consolidated standards of reporting trials (CONSORT) flow diagram of the study participant\\u0026rsquo;s recruitment.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eRandomization and allocation concealment\\u003c/h2\\u003e \\u003cp\\u003eParticipants were randomly assigned to one of two groups. Random tables were generated by SPSS 20.0. One hundred and twenty sealed envelopes were prepared by a statistician who did not participate in the study. The study was performed with neither patients\\u0026rsquo; nor observers\\u0026rsquo; awareness of the group to which each patient belonged. To assure concealment of allocation, numbers were kept in sealed and opaque envelopes, which were opened by an anaesthesiologist who was not involved in the study.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy interventions\\u003c/h2\\u003e \\u003cp\\u003eAfter entering the delivery room, peripheral venous access was opened in all participants, maternal heart rate, noninvasive blood pressure measurement, electrocardiography and pulse oximetry were monitored. All women were received oxygen for 3 L/min by transnasal catheter. Epidural anaesthesia were operated between L\\u003csub\\u003e2\\u003c/sub\\u003e and L\\u003csub\\u003e3\\u003c/sub\\u003e after cervical dilation up to 2\\u0026thinsp;~\\u0026thinsp;3 cm. After successful puncture, the epidural catheter was placed for 3.5 cm toward the head position and 1% lidocaine was injected for 3 ml. The epidural analgesia pump was connected, in which was 0.75% ropivacaine hydrochloride (20 ml) were diluted by normal saline up to 100 ml. All pumps were set with a bolus of 10 ml, continuous infusion amount of 8 ml/h, single dose of 4 ml, locking time of 15 min and stopped after fetal disengagement. Esketamine (0.2 mg/kg) was intravenously injected after fetal disengagement in the test group (Group E), while the placebo (normal saline) was administered in the control group (Group C). Labor analgesia was performed by the same anesthesiologist and esketamine or placebo were administrated by the same nurse anesthetist. Perinatal management was completed by the same obstetric team. Neither the subjects and the investigators were aware of the enrollment.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eOutcome measurements\\u003c/h2\\u003e \\u003cp\\u003eThe primary outcomes of the study were the incidence of PPD at one week and six weeks after delivery. The diagnosis of postpartum depression was based on the reference [13] and [14], in which the depression score (Edinburgh Postpartum Depression Scale, EPDS) and the diagnostic criteria for mental disorders are included.\\u003c/p\\u003e \\u003cp\\u003eRamsay sedation score before analgesia (T\\u003csub\\u003e0\\u003c/sub\\u003e), 5 (T\\u003csub\\u003e1\\u003c/sub\\u003e), 10 (T\\u003csub\\u003e2\\u003c/sub\\u003e), 20 (T\\u003csub\\u003e3\\u003c/sub\\u003e), 30 (T\\u003csub\\u003e4\\u003c/sub\\u003e) and 60 (T\\u003csub\\u003e5\\u003c/sub\\u003e) minutes after administration of esketamine were measured. The scoring criteria [15] were as follows: 1 point, patients were awake, feeling anxiety or irritability; 2 points, patients were awake, being cooperative, directional or quiet; 3 points, patients were awake, only being responsive to commands; 4 points, patients were asleep, being responsive quickly to tapping eyebrow or soft tone stimulation; 5 points, patients were asleep, being responsive slowly to tapping eyebrow or strong acoustic stimulation; 6 points, patients were asleep, being no responsive to tapping eyebrow or strong acoustic stimulation.\\u003c/p\\u003e \\u003cp\\u003eAll women were tested levels of norepinephrine (NE), epinephrine (E) ,C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-10 (IL-10) in peripheral venous blood before labor analgesia (when the woman was quiet in the ward), at 24 hours, 1 week, and 6 weeks after delivery. Serum concentrations of IL-6 and IL-10 were determined by enzyme linked immunosorbent assay (ELISA).\\u003c/p\\u003e \\u003cp\\u003eThe volume of postpartum hemorrhage was calculated for 24 hours after delivery. Side effects such as nightmares, drowsiness, nausea and vomiting were measured for 48 hours after delivery as well.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eThe statistical analysis were performed using SPSS software package (version 25.0; IBM, Inc., Chicago, IL, USA). The continuous data were presented as mean (M)\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation (SD) and examined by independent t-test. The categorical data were shown as n(%) and examined with a Chi-square test. It was considered statistically significant since a p value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePatient recruitment\\u003c/h2\\u003e \\u003cp\\u003eIn the study, a total of 120 participants were enrolled initially and three participants were excluded during the trial. One case was excluded for failure of epidural puncture, and another one was for changed to cesarean section in Group E, while one participant was excluded for failure of epidural puncture in Group C. Finally, There were 117 participants included in the statistical analysis (58 in Group E and 59 in Group C, respectively. Figure\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e, CONSORT flow diagram).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePatient characteristics\\u003c/h2\\u003e \\u003cp\\u003eThere were no significant difference of the patient characteristics (age, heigh, weight, BMI, gestational week, volume of postpartum hemorrhage) between the two groups (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eBaseline characteristics of the studied groups\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCharacteristic\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup E\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;58)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eGroup C\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;59)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP-\\u003c/em\\u003evalue \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge (years)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e28.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e27.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.656\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGestational age (weeks)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e38.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e39.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.338\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHeight (cm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e159.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e157.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.419\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eWeight (kg)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e67.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e66.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.813\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBMI (kg/m\\u003csup\\u003e2)\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e28.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e27.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.249\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePostpartum hemorrhage (ml)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e216.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;33.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e202.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;39.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.825\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eData presented as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;Standard Deviation\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eBMI: Body mass index\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003e\\u003csup\\u003ea\\u003c/sup\\u003e Independent sample t-test\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec13\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eRamsay sedation score\\u003c/h2\\u003e \\u003cp\\u003eThere were no significant difference of the Ramsay sedation score at T\\u003csub\\u003e0\\u003c/sub\\u003e and T\\u003csub\\u003e5\\u003c/sub\\u003e between the two groups. Compared with Group C, the Ramsay sedation score at T\\u003csub\\u003e1\\u003c/sub\\u003e, T\\u003csub\\u003e2\\u003c/sub\\u003e, T\\u003csub\\u003e3\\u003c/sub\\u003e and T\\u003csub\\u003e4\\u003c/sub\\u003e were significantly higher in Group E (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eRamsay sedation score in the two groups\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"7\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGroup\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eT\\u003csub\\u003e0\\u003c/sub\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eT\\u003csub\\u003e1\\u003c/sub\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eT\\u003csub\\u003e2\\u003c/sub\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eT\\u003csub\\u003e3\\u003c/sub\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eT\\u003csub\\u003e4\\u003c/sub\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eT\\u003csub\\u003e5\\u003c/sub\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGroup E\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.65\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.38\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.48\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.45\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2.57\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.51\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.64\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.49\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e2.58\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.52\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1.72\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.43\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGroup C\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.71\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.44\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.85\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.41\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2.07\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.43\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.12\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.38\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e2.08\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.42\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1.75\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.40\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP-\\u003c/em\\u003evalue \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.218\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.001\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.003\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.006\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.005\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0.556\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003eData presented as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;Standard Deviation\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003e\\u003csup\\u003ea\\u003c/sup\\u003e Independent sample t-test\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec14\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eIncidence of PPD and side effects\\u003c/h2\\u003e \\u003cp\\u003eThe incidence of PPD was significantly decreased both for one week and six weeks after delivery in Group E (3.4% vs 15.3%, p\\u0026thinsp;=\\u0026thinsp;0.004 and 5.2% vs 18.6%, p\\u0026thinsp;=\\u0026thinsp;0.006, respectively).The incidence of side effects after delivery were similar between the two groups (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eOccurrence of PPD and side effects in the two groups\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"6\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eGroup\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003ePPD\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003enausea, vomiting\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003edrowsiness\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003enightmares\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1 week\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e6 weeks\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGroup E\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2(3.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3(5.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2(3.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1(1.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e2(3.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGroup C\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9(15.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11(18.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1(1.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1(1.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e3(5.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP-\\u003c/em\\u003evalue \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.004\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.006\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.695\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.784\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.815\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003eData presented as number (percentage)\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003ePPD: postpartum depression\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003e\\u003csup\\u003ea\\u003c/sup\\u003e Chi square\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec15\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eLevels of NE, E, CRP, IL-6 and IL-10\\u003c/h2\\u003e \\u003cp\\u003eThere were no significant difference of the levels of NE, E, CRP, IL-6 and IL-10 between the two groups before labor analgesia and 6 weeks after delivery. Compared with Group C, the levels of NE, E, CRP and IL-6 were significantly lower for 24 hours and 1 week after delivery in Group E, while IL-10 were higher at the same time (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab4\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 4\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eLevels of NE, E CRP, IL-6 and IL-10 in the two groups\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"6\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVariables\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eBefore analgesia\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e24 h after delivering\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1st week after delivering\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e6th week after delivering\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eNE\\u003c/p\\u003e \\u003cp\\u003e(nmol/L)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup E\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4.36\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.77\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3.11\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.54\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.95\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.49\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e3.06\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.54\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup C\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4.58\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.84\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e4.24\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.71\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e4.15\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.73\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e3.31\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.61\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003ep\\u003c/em\\u003e value\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.629*\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.009*\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.004*\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.428*\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eE\\u003c/p\\u003e \\u003cp\\u003e(pmol/L)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup E\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e526.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;38.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e367.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;29.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e339.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;24.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e326.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;23.3\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup C\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e549.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;44.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e481.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;37.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e477.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;33.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e341.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;28.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP-\\u003c/em\\u003evalue \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.858\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.001\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.006\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.359\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eCRP\\u003c/p\\u003e \\u003cp\\u003e(mg/L)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup E\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.52\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.69\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e7.87\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.38\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e6.35\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.12\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e2.84\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.81\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup C\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.47\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.75\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e10.98\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.76\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e8.27\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.33\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e3.02\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.94\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP-\\u003c/em\\u003evalue \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.228\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.008\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.005\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.656\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eIL\\u0026minus;6\\u003c/p\\u003e \\u003cp\\u003e(ng/L)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup E\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e78.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e145.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;12.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e108.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;11.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e81.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup C\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e76.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e186.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;15.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e141.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;12.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e79.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP-\\u003c/em\\u003evalue \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.326\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.007\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.002\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.526\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eIL\\u0026minus;10\\u003c/p\\u003e \\u003cp\\u003e(\\u0026micro;g/L)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup E\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e8.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e10.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e13.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup C\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e16.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e5.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e6.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e15.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;6.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP-\\u003c/em\\u003evalue \\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.916\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.004\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.005\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.778\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003eData presented as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;Standard Deviation\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003eNE: norepinephrine; E: epinephrine; CRP: C-reactive protein; IL-6: interleukin-6; IL-10: interleukin-10\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003e\\u003csup\\u003ea\\u003c/sup\\u003e Independent sample t-test\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003eIn the study, a total of 120 participants were enrolled initially and three participants were excluded during the trial. Finally, There were 117 participants included in the statistical analysis (58 in Group E and 59 in Group C, respectively). CONSORT: the Consolidated Standards of Reporting Trials.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003ePain in the perinatal period is one of the factors leading to the development of PPD. The symptoms of PPD are more prominent in women who experience frequent pain during childbirth [16]. Although maternal pain can be relieved by labor analgesia, psychological degeneration, emotional vulnerability, stress response and inflammation may also lead to a high occurrence of PPD [17]. The results of this study showed that single intravenous injection of esketamine decreased the occurrence of PPD for one week and six weeks after delivery in women underwent labor analgesia without increasing related side effects.\\u003c/p\\u003e \\u003cp\\u003eThe traditional treatment for depression is to increase the amount of serotonin in the synaptic space to achieve the effect of alleviating depression, but these antidepressants are slow to act, generally taking three to six weeks to achieve therapeutic effects [18]. In 2019, the U. S. Food and Drug Administration (FDA) granted esketamine for the treatment of major depressive disorder and drug-resistant depression with urgent suicide risk. The results of a meta-analysis indicated that esketamine can significantly improve the patients' low mood, low self-evaluation, and even weaken the suicidal ideation, especially improve the therapeutic effect for treatment resistant depression (TRD) [19].\\u003c/p\\u003e \\u003cp\\u003eAnother retrospective analysis have showed that both esketamine's approval for use in TRD and longer-term safety data may position it preferentially above racemic ketamine, though the efficacy of esketamine compared to racemic ketamine remained unclear [20]. However, there are few studies on esketamine used in postpartum depression. Our previous studies indicated that the incidence of PPD was reduced by prophylactic intravenous use of esketamine or combined with patient control intravenous analgesia for women underwent cesarean section [11, 12]. The study of Wang et al [21] also have showed that the application of esketamine after cesarean section can effectively reduce depression-related scores and the risk of postpartum depression without increasing adverse reactions and had high safety. However, a lower dose of esketamine was used in our study. Based on previous studies, we applied esketamine to the prevention of postpartum depression in labor analgesia and achieved certain results in this study.\\u003c/p\\u003e \\u003cp\\u003eAs endocrine hormones, NE and E can affect the the bodys\\u0026rsquo; mood by modulating the sensitivity of neuronal synapses and neurotransmitters [22]. NE can return to the synaptic space under the action of NE transporter protein, and also form E by acting on phenylmethylamine-N-methyltransferase, which easily lead to fear and tension [23]. It had been reported that the blue spot located in the brain stem was activated due to the changes in stress and hormone levels during pregnancy, thus releasing a large number of NE to participate in the regulation of the nervous system, which was easy to cause tension and depression [24]. In this study, the levels of NE and E were significantly lower at 24 hours and 1 week after delivery in Group E than in Group C, which also suggested that the maternal stress response was decreased in the tested group. The antidepressant mechanism may be the target of esketamine for monoaminergic nervous system, can affect the brain stem blue spot, and further affect the noradrenergic system, promote the transcription and expression of the gene, increase the synthesis of transporter, resulting in NE migration from plasma membrane to cytoplasm, decrease the concentration of serum NE and E [25]. Additionally, due to the sedative and analgesic effects of esketamine, the Ramsay sedation score was decreased at 5, 10, 20 and 30 minutes after administration of esketamine in this study, which might be one of the reasons for the reduced stress response in the tested group.\\u003c/p\\u003e \\u003cp\\u003eAs a non-specific inflammatory marker, CRP reflects the stress and inflammation response of the human body. When infection and injury take palce, CRP rises sharply in the plasma [26]. Besides, among the inflammatory mediators released by the human body under pain and traumatic stress, IL-6 is the earliest and highly sensitive proinflammatory factor expressed, which is closely related to the size of trauma, body immune status and prognosis [27]. IL-10 is an inflammatory suppressor, which can exert an anti-inflammatory effect by inhibiting nuclear factors activity and promoting neutrophil apoptosis to reduce pro-inflammatory factors [28]. Therefore, the levels of CRP, IL-6 and IL-10 were observed in the present study to measure the effects of esketamine on inflammatory response. In this study, the levels of CRP and IL-6 were significantly lower at 24 hours and 1 week after delivery in the tested group, while IL-10 were higher at the same time. This results indicated that the antidepressant effect of esketamine might be related to the reduced inflammatory response in puerperants underwent labor analgesia.\\u003c/p\\u003e \\u003cp\\u003eStudies have shown the brain causes negative emotions by the clustering of the lateral halterate nucleus, where the excitatory transmitter is the N-methyl-D-aspartate (NMDA) receptor of the glutamate-gated ion channel[29, 30]. As a blocker of the glutamate-gated ion channel NMDA receptor, the main antidepressant mechanism of esketamine is to sustainable block the NMDA receptor, block the elongation factor 2 (eEF 2) kinase, increase the release of brain-derived neurotrophic factor (BDNF) and the expression of tropomyosin receptor kinase B (TrkB), induce rapamycin target complex 1 (mTORC1) signaling pathway and extracellular regulatory protein kinase (ERK) activation, improve neuroplasticity and synapse formation [31, 32]. In short, the traditional treatment of antidepression drugs is to stimulate the \\u0026ldquo;reward center\\\" of the brain, while esketamine is to remove the inhibitory effect of the \\\"reward center\\u0026rdquo;.\\u003c/p\\u003e \\u003cp\\u003eEsketamine has been used clinically for many years as an anesthetic drug, but the evidence is still insufficient as an antidepressant drug. Considering the possible side effects such as nightmare, hallucination and abusement, esketamine was used only once in the study and was lower than the subanesthetic dose. In addition, through the follow-up after delivery, we found that the adverse reactions did not increase in the test group.\\u003c/p\\u003e \\u003cp\\u003eThere were some limitations in this study, such as the strong subjectivity of the PPD evaluation by EPDS. To minimize the subjective differences, the PPD valuator in this study was the same physician who did not participate in the specific study. Furthermore, the objective indicators such as levels of, NE, E, CRP, IL\\u0026minus;6 and IL\\u0026minus;10 were also combined in the study, which could better reflect maternal depression. Furthermore, the severity of PPD was not measured in this study, which would be content of next studies.\\u003c/p\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eIn conclusion, single intravenous injection of esketamine (0.2 mg/kg) after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026rsquo; contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eBL, YZ, HX and WW designed the study. QWsupervised the practical carrying out of the clinical trial. WY participated in the study\\u0026rsquo;s conceptualization and sampling.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026nbsp;ZY and HX analyzed the data. BL, YZ and WW wrote the manuscript. All authors read and approved the final manuscript.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNo funding was received for conducting this study.\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets used and analyzed during the current study are available from\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003ethe corresponding author on reasonable request. Wei Wang, e-mail: wangwei2024@163.com.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study was performed in accordance with the declaration of Helsinki. Ethical approval for this study (2021-03-031-K01) was provided by the Institutional Ethics Committee of the Affiliated Jiangning Hospital of Nanjing Medical University. The registration of this study was approved in the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number\\u0026mdash;ChiCTR2200060387). All volunteers involved were informed of the proposal and gave their written, informed consent.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot Applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no conflict of interests.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003ePPD \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;postpartum depression\\u003c/p\\u003e\\n\\u003cp\\u003eASA \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; American society of Aneshesiologists\\u003c/p\\u003e\\n\\u003cp\\u003eCONSORT \\u0026nbsp; \\u0026nbsp;consolidated standards of reporting trials\\u003c/p\\u003e\\n\\u003cp\\u003eEPDS \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;Edinburgh Postpartum Depression Scale\\u003c/p\\u003e\\n\\u003cp\\u003eNE \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;norepinephrine\\u003c/p\\u003e\\n\\u003cp\\u003eE \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; epinephrine\\u003c/p\\u003e\\n\\u003cp\\u003eCRP \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;C-reactive protein\\u003c/p\\u003e\\n\\u003cp\\u003eIL-6 \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;interleukin-6\\u003c/p\\u003e\\n\\u003cp\\u003eIL-10 \\u0026nbsp; \\u0026nbsp; \\u0026nbsp; interleukin-10\\u003c/p\\u003e\\n\\u003cp\\u003eNMDA \\u0026nbsp; \\u0026nbsp; \\u0026nbsp;N-methyl-D-aspartate\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eZhao P, Cai Z, Huang A, Liu C, Li H, Yang S, Hu LQ. Why is the labor epidural rate low and cesarean delivery rate high? A survey of Chinese perinatal care providers. PLoS One. 2021; 16(5):e0251345.\\u003c/li\\u003e\\n\\u003cli\\u003eWedajo LF, Alemu SS, Jarso MH, Golge AM, Dirirsa DE. Late postpartum depression and associated factors: community-based cross-sectional study. BMC Womens Health. 2023; 23(1):280.\\u003c/li\\u003e\\n\\u003cli\\u003ePingeton BC, Cochran A, Goodman SH, Laurent H, Sbrilli MD, Knight B, et al. Positive affect improves a transdiagnostic model of perinatal depression symptoms. J Affect Disord. 2023; 336:112-119.\\u003c/li\\u003e\\n\\u003cli\\u003eSerra R, Giacchetti N, Bersani FS, Cappannini G, Martucci M, Panfili M, et al. The relationship between personality traits and individual factors with perinatal depressive symptoms: a cross-sectional study. BMC Pregnancy Childbirth. 2023; 23(1):382.\\u003c/li\\u003e\\n\\u003cli\\u003eBales M, Pambrun E, Maguet C, van der Waerden J, Glangeaud-Freudenthal N, Charles MA, et al. Pathways between Risk/Protective Factors and Maternal Postnatal Depressive Symptoms: The ELFE Cohort. J Clin Med. 2023; 12(9):3204.\\u003c/li\\u003e\\n\\u003cli\\u003eAlmutairi HA, Alyousef SM, Alhamidi SA, Almoammar DN. Exploring the Healthcare Services\\u0026apos; Contribution to Reducing Postpartum Depression. SAGE Open Nurs. 2023; 9:23779608231171780.\\u003c/li\\u003e\\n\\u003cli\\u003eHorwitz AB, Rubin RT. Barbiturates and pyrazolopyridines for the treatment of postpartum depression-repurposing of two drug classes. Front Pharmacol. 2023; 14:1139889.\\u003c/li\\u003e\\n\\u003cli\\u003eChen-Li D, Lui LMW, Rosenblat JD, Lipsitz O, Teopiz KM, Ho R, et al. Ketamine as potential treatment for postpartum depression: A narrative review. Ann Clin Psychiatry. 2022; 34(4):264-274.\\u003c/li\\u003e\\n\\u003cli\\u003eWłodarczyk A, Dywel A, Cubała WJ. Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms. Pharmaceuticals (Basel). 2023; 16(2):173.\\u003c/li\\u003e\\n\\u003cli\\u003eVasiliu O. Esketamine for treatment‑resistant depression: A review of clinical evidence (Review). Exp Ther Med. 2023; 25(3):111.\\u003c/li\\u003e\\n\\u003cli\\u003eWang W, Xu H, Ling B, Chen Q, Lv J, Yu W. Effects of esketamine on analgesia and postpartum depression after cesarean section: A randomized, double-blinded controlled trial. Medicine (Baltimore). 2022;101(47):e32010.\\u003c/li\\u003e\\n\\u003cli\\u003eWang W, Ling B, Chen Q, Xu H, Lv J, Yu W. Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial. Medicine (Baltimore). 2023; 102(9): e33086.\\u003c/li\\u003e\\n\\u003cli\\u003eSrisurapanont M, Oon-Arom A, Suradom C, Luewan S, Kawilapat S. Convergent Validity of the Edinburgh Postnatal Depression Scale and the Patient Health Questionnaire (PHQ-9) in Pregnant and Postpartum Women: Their Construct Correlations with Functional Disability. Healthcare (Basel). 2023; 11(5):699.\\u003c/li\\u003e\\n\\u003cli\\u003eKammerer M, Marks MN, Pinard C, Taylor A, von Castelberg B, K\\u0026uuml;nzli H, et al. Symptoms associated with the DSM IV diagnosis of depression in pregnancy and post partum. Arch Womens Ment Health. 2009; 12(3):135-41.\\u003c/li\\u003e\\n\\u003cli\\u003eZaki HA, Ibrahim T, Osman A, Elnabawy WA, Gebril A, Hamdi AH, et al. Comparing the Safety and Effectiveness of Ketamine Versus Benzodiazepine/Opioid Combination for Procedural Sedation in Emergency Medicine: A Comprehensive Review and Meta-Analysis. Cureus. 2023; 15(3):e36742.\\u003c/li\\u003e\\n\\u003cli\\u003eLevin G, Ein-Dor T. A unified model of the biology of peripartum depression. Transl Psychiatry. 2023; 13(1):138.\\u003c/li\\u003e\\n\\u003cli\\u003eDu W, Bo L, Xu Z, Liu Z. Childbirth Pain, Labor Epidural Analgesia, and Postpartum Depression: Recent Evidence and Future Directions. J Pain Res. 2022; 15:3007-3015.\\u003c/li\\u003e\\n\\u003cli\\u003eWitkin JM, Golani LK, Smith JL. Clinical pharmacological innovation in the treatment of depression. Expert Rev Clin Pharmacol. 2023; 16(4):349-362.\\u003c/li\\u003e\\n\\u003cli\\u003eFloriano I, Silvinato A, Bernardo WM. The use of esketamine in the treatment of patients with severe depression and suicidal ideation: systematic review and meta-analysis. Rev Assoc Med Bras (1992). 2023; 69(4):e2023D694.\\u003c/li\\u003e\\n\\u003cli\\u003eSwainson J, Thomas RK, Archer S, Chrenek C, MacKay MA, Baker G, et al. Esketamine for treatment resistant depression. Expert Rev Neurother. 2019; 19(10):899-911.\\u003c/li\\u003e\\n\\u003cli\\u003eWang Q, Xiao M, Sun H, Zhang P. A Study on the Preventive Effect of Esketamine on Postpartum Depression (PPD) after Cesarean Section. Comput Math Methods Med. 2022; 2022:1524198.\\u003c/li\\u003e\\n\\u003cli\\u003ePeacock BN, Scheiderer DJ, Kellermann GH. Biomolecular aspects of depression: A retrospective analysis. Compr Psychiatry. 2017; 73:168-180.\\u003c/li\\u003e\\n\\u003cli\\u003eWang P, Yan F, Dong J, Wang S, Shi Y, Zhu M, et al. A multiple-step screening protocol to identify norepinephrine and dopamine reuptake inhibitors for depression. Phys Chem Chem Phys. 2023; 25(12):8341-8354.\\u003c/li\\u003e\\n\\u003cli\\u003eMeng Q, Garcia-Garcia AL, Dranovsky A, Leonardo ED. Inhibition of norepinephrine signaling during a sensitive period disrupts locus coeruleus circuitry and emotional behaviors in adulthood. Sci Rep. 2023 13(1):3077.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu H, Lan X, Wang C, Zhang F, Fu L, Li W, et al. The efficacy and safety of esketamine in the treatment of major depressive disorder with suicidal ideation: study protocol for a randomized controlled trial. BMC Psychiatry. 2022; 22(1):744.\\u003c/li\\u003e\\n\\u003cli\\u003eFilep JG. Targeting conformational changes in C-reactive protein to inhibit pro-inflammatory actions. EMBO Mol Med. 2023; 15(1):e17003.\\u003c/li\\u003e\\n\\u003cli\\u003eYeh MSL, Poyares D, D\\u0026apos;Elia ATD, Coimbra BM, Mello AF, Tufik S, et al. Sleep characteristics and inflammatory markers in women with post-traumatic stress disorder. BMC Psychiatry. 2023; 23(1):273.\\u003c/li\\u003e\\n\\u003cli\\u003eNagata K, Nishiyama C. IL-10in Mast Cell-Mediated Immune Responses: Anti-Inflammatory and Proinflammatory Roles. Int J Mol Sci. 2021; 22(9):4972.\\u003c/li\\u003e\\n\\u003cli\\u003eZanos P, Brown KA, Georgiou P, Yuan P, Zarate CA Jr, Thompson SM, et al. NMDA Receptor Activation-Dependent Antidepressant-Relevant Behavioral and Synaptic Actions of Ketamine. J Neurosci. 2023; 43(6):1038-1050.\\u003c/li\\u003e\\n\\u003cli\\u003eChen R, Capit\\u0026atilde;o LP, Cowen PJ, Harmer CJ. Effect of the NMDA receptor partial agonist, d-cycloserine, on emotional processing and autobiographical memory. Psychol Med. 2021; 51(15):2657-2665.\\u003c/li\\u003e\\n\\u003cli\\u003ed\\u0026apos;Andrea G, Pettorruso M, Lorenzo GD, Mancusi G, McIntyre RS, Martinotti G. Rethinking ketamine and esketamine action: Are they antidepressants with mood-stabilizing properties? Eur Neuropsychopharmacol. 2023; 70:49-55.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu B, Du Y, Xu C, Liu Q, Zhang L. Antidepressant effects of repeated s-ketamine administration as NMDAR Antagonist: Involvement of CaMKII\\u0026alpha; and mTOR signaling in the hippocampus of CUMS mice. Brain Res. 2023; 1811:148375.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-pharmacology-and-toxicology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"phat\",\"sideBox\":\"Learn more about [BMC Pharmacology and Toxicology](http://bmcpharmacoltoxicol.biomedcentral.com)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/phat/Default.aspx\",\"title\":\"BMC Pharmacology and Toxicology\",\"twitterHandle\":\"@BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Esketamine, Depression, Postpartum, Analgesia, Obstetrical\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-3100226/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-3100226/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground：\\u003c/strong\\u003eThe study was designed to investigate effects of single intravenous injection\\u003cstrong\\u003e \\u003c/strong\\u003eof\\u003cstrong\\u003e \\u003c/strong\\u003eesketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods：\\u003c/strong\\u003eA total of\\u003cstrong\\u003e \\u003c/strong\\u003e120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 hours, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults：\\u003c/strong\\u003eThe incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs 15.3%, p = 0.004 and 5.2% vs 18.6%, p = 0.006, respectively) . There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 hours after delivery were similar between the two groups.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions：\\u003c/strong\\u003eSingle\\u003cstrong\\u003e \\u003c/strong\\u003eintravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Effect of Single Intravenous Injection of Esketamine on Postpartum Depression after Labor Analgesia and Potential Mechanisms: A Randomized, Double-blinded Controlled Trial\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2023-06-30 18:12:11\",\"doi\":\"10.21203/rs.3.rs-3100226/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Major revision\",\"date\":\"2023-08-04T13:37:31+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2023-08-02T21:17:10+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2023-06-28T08:04:49+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Pharmacology and Toxicology\",\"date\":\"2023-06-23T11:52:56+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-pharmacology-and-toxicology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"phat\",\"sideBox\":\"Learn more about [BMC Pharmacology and Toxicology](http://bmcpharmacoltoxicol.biomedcentral.com)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/phat/Default.aspx\",\"title\":\"BMC Pharmacology and Toxicology\",\"twitterHandle\":\"@BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"04a2b08b-c269-4ad2-a326-f475bc1d807f\",\"owner\":[],\"postedDate\":\"June 30th, 2023\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2023-11-27T15:04:52+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-3100226\",\"link\":\"https://doi.org/10.1186/s40360-023-00705-7\",\"journal\":{\"identity\":\"bmc-pharmacology-and-toxicology\",\"isVorOnly\":false,\"title\":\"BMC Pharmacology and Toxicology\"},\"publishedOn\":\"2023-11-23 15:01:39\",\"publishedOnDateReadable\":\"November 23rd, 2023\"},\"versionCreatedAt\":\"2023-06-30 18:12:11\",\"video\":\"\",\"vorDoi\":\"10.1186/s40360-023-00705-7\",\"vorDoiUrl\":\"https://doi.org/10.1186/s40360-023-00705-7\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-3100226\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-3100226\",\"identity\":\"rs-3100226\",\"version\":[\"v1\"]},\"buildId\":\"FbvkV6FR0MCFSLy54lSbu\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}