Effect of esketamine on postpartum depression and pain control after caesarean section: A randomized, double-blind, controlled clinical trial

Effect of esketamine on postpartum depression and pain control after caesarean section: A randomized, double-blind, controlled clinical 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 esketamine on postpartum depression and pain control after caesarean section: A randomized, double-blind, controlled clinical trial Shurong Li, Zhifang Zhuo, Renwei Li, Kaikai Guo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3507701/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Feb, 2024 Read the published version in BMC Anesthesiology → Version 1 posted 11 You are reading this latest preprint version Abstract Background Postpartum depression (PPD) after cesarean delivery is a common complication. Esketamine's effects on PPD in women undergoing cesarean section remain contradictory, despite ketamine's prophylactic effects. This study evaluated the effect of esketamine as an adjunct to patient-controlled intravenous analgesia (PCIA) to prevent PPD in women undergoing caesarean section. Methods A total of 275 parturients scheduled for caesarean section and subsequent PCIA were recruited from a single centre and randomised to control (sufentanil 2 µg/kg + tropisetron 10 mg) or esketamine (additional esketamine 1.5 mg/kg). The primary outcome was the incidence of PPD, as measured by the Edinburgh postnatal depression scale (EPDS), following surgery. Secondary outcomes were cumulative sufentanil consumption, numerical rating scale (NRS) scores, stress hormone levels and biomarkers of PPD. Results A total of 246 postpartum women with caesarean delivery were included in the final analysis. The incidence of depression among parturients on postoperative day 42 was higher in the control group compared to the esketamine group, with rates of 17.6% and 8.2% respectively (P = 0.02). The EPDS scores were significantly higher in the control group, with a mean score of 9.02 ± 2.21 vs. 6.87 ± 2.14 in the esketamine group (p < 0.0001). Sufentanil consumption was significantly lower in the esketamine group in the 0–24 h (42.5 ± 4.58 µg vs 50.15 ± 5.47 µg, P = 0.04) and 0–48 h (87.40 ± 9.51 µg vs 95.10 ± 9.36 µg, P = 0.04) postoperative periods compared to the control group. Significant differences in movement were observed between the two groups at 24 and 48 hours after cesarean section (3.39 ± 1.57 vs 4.50 ± 0.80, P = 0.02; 2.43 ± 0.87 vs 3.56 ± 0.76, P = 0.02). Furthermore, the plasma level of stress hormone was significantly lower on postoperative day 3 in the esketamine group compared to the control group. The frequency of side effects observed in both groups was comparable. Conclusions Esketamine (1.5 mg/kg) used as a supplement in PCIA significantly decreases the occurrence of PPD in 42 days and reduced cumulative sufentanil consumption in a span of 48 hours post-cesarean operation, without raising the rate of adverse effects. Trial registration: Registered in the Chinese Clinical Trial Registry (ChiCTR2200067054) on December 26, 2022. Esketamine Cesarean section Patient-controlled intravenous analgesia Postpartum depression Postpartum women Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Postpartum depression (PPD) is a prevalent psychological condition seen in females during the perinatal phase, characterized by a frequency ranging from 10–20%. Notably, the prevalence of PPD tends to be greater in middle and low-income nations [1]. PPD has been seen appear within a range of timeframes after childbirth, including as early as 6 weeks postpartum or later at 3, 6, 12, and even up to 36 months after delivery [2, 3]. Symptoms associated with PPD include feelings of sadness, a persistent state of low mood, diminished appetite, decreased interest in previously enjoyed activities, psychomotor retardation, and disturbances in sleep patterns. Severe PPD has been shown to be associated with an increased risk of suicidal thoughts [4]. PPD has negative effects on both newborns and family connections. Additionally, it places a substantial demand on medical services and resources [5, 6]. The effectiveness of pharmaceutical therapies for PPD is restricted owing to their delayed start of action and poor treatment effectiveness, despite their frequent use [7, 8]. Furthermore, it is worth noting that there are now no pharmacological interventions available for PPD. Ketamine, a dissociative anesthetic, functions as an antagonist of the N-methyl-D-aspartate receptor (NMDAR), which can elicit prompt and enduring antidepressant properties in individuals with depression who have not responded to conventional treatments [9, 10]. The preventive benefits of ketamine against PPD were observed in Chinese women following cesarean section because it decreased PPD when administered intravenously at a dosage of 0.5mg/kg [5]. Nevertheless, the utilization of ketamine in a therapeutic setting as an antidepressant is constrained by its adverse effects, which include dissociative and psychotomimetic manifestations, as well as the potential for addiction [11–13]. The anesthetic impact of esketamine, a ketamine dextral resolution, has been shown to be twofold more than that of the (R, S)-ketamine mixture and nearly thrice greater than that of (R)-ketamine [14]. Additionally, the incidence of adverse effects associated with esketamine was found to be decreased compared to subanesthetic dosages of ketamine [15]. Multiple clinical investigations have provided evidence supporting the notion that the perioperative intravenous (IV) injection of ketamine has the potential to decrease the occurrence of PPD [16, 17]. The administration of esketamine by IV means at doses of 0.2 and 0.4 mg/kg resulted in prompt and persistent antidepressant impacts in individuals with depression who were unresponsive to conventional treatments [17]. The study conducted by Han et al. (2022) provided evidence supporting the use of esketamine (0.01 mg/kg/h) as an adjuvant in patient-controlled intravenous analgesia (PCIA) to decrease the occurrence of PPD during a two-week period following cesarean section [18]. In addition, Wang and colleagues (2022a) have shown that the administration of esketamine (at doses of 0.1, 0.2, or 0.4 mg/kg) in combination with sufentanil for PCIA resulted in a decrease in the occurrence of PPD, the usage of sufentanil [19]. It seems that the administration of esketamine during the perioperative period may have a preventive effect on the occurrence of PPD after cesarean surgery. However, in a randomized controlled trial, the authors found that the esketamine administration at a dosage of 0.5 mg/kg/h for intraoperative analgesia, as well as esketamine administration at a dosage of 1.25 mg/kg as an adjunct in PCIA, did not result in a reduction in the incidence of PPD risk among women who underwent elective cesarean section [16]. Hence, the existing body of data is deemed inadequate owing to notable variations in the size of the study population, the time and dosage of esketamine administration, and the presence of confounding factors like body mass index (BMI), socioeconomic level, and the specific method of cesarean section. The objective of this investigation was to investigate the preventive impact of a higher dose of esketamine infusion (1.5 mg/kg) as a supplementary treatment in PCIA on the risk of PPD in Chinese females following planned cesarean section. The assessment of PPD risk was determined by evaluating screening outcomes, specifically focusing on individuals who obtained an EPDS score of 13 or above. This approach was used instead of relying on prospective formal diagnoses or comprehensive evaluations of medical records. The analgesic effects of esketamine on the parturients after surgery were also explored in our study. Furthermore, we measured the stress hormone levels including free cortisol (FC), atrial natriuretic peptide (ANP), epinephrine (E) and norepinephrine (NE), and PPD biomarkers (e.g. interleukin-6 [IL-6], C-reactive protein [CRP], and brain-derived neurotrophic factor [BDNF]) in the blood since these markers are revealed to have a function in PPD and antidepressant impact of ketamine [20, 21]. Methods The present study was a prospective, double-blind, randomized controlled experiment that took place at the First Hospital of Putian City in China from September 2022 to July 2023. The annual number of births is around 2000, with cesarean deliveries accounting for 600 of these cases. The research received ethical permission (2022-026) from the Institutional Ethics Committee of the First Hospital of Putian City. Additionally, it was recorded in the Chinese Clinical Trial Registry (ID: ChiCTR2200067054) on 26/12/2022. Prior to the beginning of the trial, everyone who participated in the research gave informed permission. A total of 246 maternity women who were classified as American Society of Anesthesiologists physical status II, aged between 19 and 44 years, and having elective surgical operations under general anesthesia were included in the investigation. The criteria for exclusion were as follows: (1) mental disorder; (2) serious obstetric problems or underlying medical conditions; (3) esketamine allergy; and (4) ineligibility for intraspinal anesthesia. In accordance with the findings obtained from our preliminary experiment, which had a sample size of 20 individuals in each group, the pre-test data indicated that the prevalence of PPD was 24% in the placebo group and 10% in the esketamine group. The sample size needed for each group was determined to be 110 individuals, based on a power of 80% and a significance level of 5%. This calculation was performed employing the PASS 15.0 program developed by Stata Corp. LP, located in College Station, TX, USA. In order to account for an expected participant dropout rate of 10%, it was determined that each arm of the study would have 120 individuals. The flow chart of the research participants' recruitment is shown in Fig. 1 , illustrating the Consolidated Standards of Reporting Trials. The subjects were randomized to two groups, namely the esketamine and the control groups, in a random manner, with an equal number of participants in each group. The esketamine group received esketamine, while the control group received normal saline. The process of simple randomization was performed utilizing IBM SPSS program version 26.0 (SPSS Inc., Chicago, IL, USA). This program produced random numbers to allocate participants to different groups. The pharmacist made syringes filled with esketamine or a solution of normal saline. The aforementioned items were enclosed into envelopes that were numbered in consecutive order and afterwards transported to the designated operation room. The nurse sequentially opened the envelopes in accordance with their numbered order. Every individual envelope was found to contain a syringe. The randomization assignment was concealed from both the participants and investigators in order to maintain blinding. All females who experienced delivery had spinal anesthetic at the L3-L4 or L2-L3 and subjected to PCIA after operation. The administration of the anesthetic solution, consisting of 2 mL of 1% ropivacaine and 1 mL of 10% glucose, was performed by a qualified anesthesiologist. The dosage provided was 1 mL every 5 s, with the aim of attaining the maximum degree of sensory block at the T4-T6. Following the completion of the surgical procedure, all patients were given non-steroidal anti-inflammatory medicines in the form of a 40 mg IV dose of flurbiprofen. Additionally, preemptive analgesia was provided utilizing ultrasound-guided transversus abdominis plane block. The control group in the study included a combination of 2 µg/kg sufentanil and 10 mg tropisetron. On the other hand, the esketamine group received a combination of 2 µg/kg sufentanil, 10 mg tropisetron, and esketamine at a dosage of 1.5 mg/kg. These combinations were administered in a total volume of 100 mL. All participants were administered a continuous infusion at a baseline rate of 2 mL/h, as well as a 1 mL on-demand bolus with a 15 min lockout interval. The administration of the infusion initiated instantly after the closure of the skin incision and continued for two days. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire was administered to the subjects in a face-to-face interview conducted the day before to surgical preparation. The participants were contacted by telephone or WeChat in order to finish EPDS 42 days post-cesarean section, with the aim of diagnosing PPD. EPDS, a diagnostic instrument used for detecting PPD cases [22], has undergone translation into the Chinese language to facilitate the assessment of Chinese patients [23]. The EPDS comprises a set of 10 questions, with each item carrying a maximum score of three points. Consequently, the cumulative score attainable on the EPDS equals 30 points. In the present investigation, we classified EPDS scores equal to or more than 13 as indicative of postpartum depression [24]. The main objective of the research was to assess the occurrence of PPD risk 42 days after childbirth. This was accomplished by employing the EPDS administered by means of a web-based questionnaire. The secondary outcomes assessed in the study included cumulative sufentanil consumption, postoperative pain intensity, plasma levels of stress hormone levels and PPD biomarkers, and incidence of adverse events. The total amount of sufentanil consumed throughout certain time periods after the surgical procedure, including the intervals of 0–24 h, 24–48 h, and 0–48 h. Pain severity was evaluated utilizing the numeric rating scale (NRS) score, with pain scores at rest and throughout movements documented at 2, 4, 8, 12, 24, and 48 h after cesarean delivery. The enzyme-linked immunosorbent assay was employed to detect the plasma levels of FC, ANP, E, NE, CRP, IL-6, and BDNF on the day prior to preparation of surgery and on day 3 after surgery. The blood samples were obtained between the time frame of 6 to 7 a.m. Negative side effects throughout PCIA, like headache, nausea, vomiting, dizziness, drowsiness, and itching were reported. Demographic features, like weight, height, calculated BMI, age, gestational weeks, pregnancy complications, gravidity, parity, marital status, educational level, and EPDS scores, were obtained the day prior to the operation. SPSS IBM statistical program package, version 26.0 (SPSS Inc., Chicago, IL), was employed to conduct Data analysis. Shapiro-Wilk test was utilized to detect the Normality assumptions for continuous variables. The independent sample t-test or Mann-Whitney U test were employed to test the between-group variations for continuous normally distributed variables or non-normally distributed variables, respectively. The chi-square test was employed to compare categorical variables between groups. The NRS score was quantified employing the mean and standard deviation, and the variations between groups were assessed by repeated measures analysis of variance (ANOVA), and multiple comparisons were analyzed by Bonferroni adjustment. The observed results were deemed to be statistically significant, as shown by a p-value of less than 0.05. Results Typically, 360 parturients were enrolled between January 1, 2023, and September 31, 2023. Of these, 36 refused to receive PCIA after cesarean delivery, 12 underwent combined spinal-epidural anesthesia and general anesthesia, 16 experienced life-threatening chronic comorbid diseases, 21 participated in other clinical studies, and 275 participants were randomized into the esketamine and the control groups. Twenty-nine parturients were lost to follow-up. Consequently, the study included a total of 246 cases (Fig. 1 ). Table 1 provides a comprehensive overview of the demographic and clinical features of the patients. No statistically significant variations were observed between the two groups (Table 1 ). Table 1 Preoperative data of the included pregnant women Variables Control group Esketamine group P value Number 122 124 Age (year), mean ± SD 19–42 27.7 ± 4.8 20–44 28 ± 3.1 0.56 Pre-pregnancy BMI (kg/m2), mean ± SD 52–77 24.1 ± 3.1 52–75 24.5 ± 4.7 0.43 Gestational weeks, n (%) Full term Preterm Post term 101 (82.77) 14 (11.48) 7 (5.74) 106 (85.48) 12 (9.67) 6 (4.84) 0.85 Pregnancy complications, n (%) Gestational diabetes Gestational hypertension Gestational Low thyroid 13 (10.66) 21 (17.21) 32 (26.23) 12 (9.68) 24 (19.35) 35 (28.23) 0.84 0.74 0.78 Gravidity, n (%) 0 ≥1 47 (38.52) 75 (61.48) 50 (40.32) 74 (59.68) 0.80 Parity, n (%) 0 ≥1 61 (50) 61 (50) 65 (52.42) 59 (47.58) 0.80 Marital status, n (%) Married Divorced Unmarried 121 (99.18) 0 (0) 1 (0.82) 122 (98.39) 1 (0.81) 1 (0.81) 0.61 Educational level, n (%) Master or above Bachelor or below 43 (35.25) 79 (64.75) 50 (40.32) 74 (59.68) 0.43 Stress hormone levels, mean ± SD Free cortisol (FC) (nmol/L) 261.51 ± 55.32 251.98 ± 62.23 0.21 Atrial natriuretic peptide (ANP) (ng/mL) 0.54 ± 0.25 0.59 ± 0.19 0.08 Epinephrine (E) (ng/L) 37.09 ± 4.32 35.92 ± 5.39 0.06 Norepinephrine (NE) (ng/L) 159.82 ± 32.21 155.16 ± 43.13 0.34 Biomarkers, mean ± SD C-reactive protein (CRP) (mg/dl) 0.32 ± 0.11 0.34 ± 0.09 0.12 Interleukin-6 (IL-6) (pg/mL) 2.30 ± 0.7 2.11 ± 1.01 0.11 Brain-derived neurotrophic factor (BDNF) (pg/mL) 1.31 ± 0.09 1.29 ± 0.12 0.14 Edinburgh Postpartum Depression Scale, mean ± SD 4.0 ± 2.1 3.6 ± 3.0 0.23 The rate of depression was significantly lower in the esketamine group in contrast to that in the control group at 42 days after cesarean section (22.2% and 10.7%, P = 0.015) (Fig. 2 ). The scores of EPDS were comparable between the esketamine and control groups before operation (3.6 ± 3.0 vs. 4.0 ± 2.1, P = 0.23). Nevertheless, significant inter-group variations in scores of EPDS were detected at 42 days postpartum (6.87 ± 2.14 vs. 9.02 ± 2.21, P < 0.0001) (Fig. 2 ). The consumption of sufentanil throughout the first day (42.5 ± 4.58 µg vs 50.15 ± 5.47 µg, P = 0.04) and two days (87.40 ± 9.51 µg vs 95.10 ± 9.36 µg, P = 0.04) after surgery were significantly lower in the esketamine group than that in the control group. Nevertheless, there was no statistically significant variation observed during the 24–48 h postpartum period (43.50 ± 5.34 µg vs 46.40 ± 3.86 µg, P = 0.71) (Fig. 2 ). NRS scores at rest were unchanged in the esketamine group at 2, 4, 8, 12, 24, 48 h after cesarean section (1.11 ± 0.65 vs 1.31 ± 0.56, P = 0.49; 4.03 ± 0.94 vs 4.21 ± 0.88, P = 0.20; 3.41 ± 0.53 vs 3.32 ± 0.64, P = 0.88; 2.98 ± 0.64 vs 3.11 ± 0.73, P = 0.57; 2.86 ± 0.58 vs 3.01 ± 0.75, P = 0.40; 1.91 ± 0.62 vs 2.11 ± 0.43, P = 0.20, respectively). Contrarily, significant variations on movement were observed between both groups at 24, 48 h after cesarean section (3.39 ± 1.57 vs 4.50 ± 0.80, P = 0.02; 2.43 ± 0.87 vs 3.56 ± 0.76, P = 0.02), rather than at 12 h (4.35 ± 0.86 vs 5.32 ± 0.95, P = 0.06) (Fig. 3 ). Serum FC and ANP levels were substantially lesser in esketamine group than that in the control group (FC: 302 ± 101 vs 382 ± 91 nmol/L, P˂0.0001; ANP: 0.71 ± 0.23 vs 1.01 ± 0.42 ng/mL, P˂0.0001), and the E and NE level was significantly decreased in esketamine group in contrast to that in the control group (E: 39.47 ± 4.58 vs 54.32 ± 6.19 ng/L, P˂0.0001; NE: 160.84 ± 39.45 vs 190.31 ± 43.29 ng/L, P˂0.0001) (Fig. 4 ). There was no statistically significant difference seen in the plasma concentrations of CRP and IL-6 between both groups on the third day following the surgical procedure (CRP: 1.23 ± 0.32 vs 1.19 ± 0.29 mg/ml, P = 0.31; IL-6: 8.01 ± 1.12 vs 7.92 ± 0.91 pg/mL, P = 0.49, respectively). Likewise, there were no statistically significant variations observed in the plasma concentrations of BDNF among both groups (1.32 ± 0.62 vs 1.45 ± 0.44 pg/mL, P = 0.06) (Fig. 5 ). The predominant side effects seen in the placebo group during the surgical procedure were nausea and vomiting (27.42%), dizziness (16.94%), pruritus (8.84%), and drowsiness (2.41%). Esketamine group were nausea and vomiting (25.41%), dizziness (22.95%), pruritus (6.56%), and drowsiness (0.82%). There were no statistically significant variations observed in the occurrence of adverse events between both groups (P > 0.05, Table 2 ). Table 2 Analgesia-related adverse events, n (%) Variables Control group Esketamine group P value Nausea and vomiting 31(25.41) 34(27.42) 0.77 Dizziness 28(22.95) 21(16.94) 0.27 Pruritus 8(6.56) 6(8.84) 0.59 Drowsiness 1(0.82) 3(2.41) 0.62 Discussion The findings of this randomized controlled investigation indicate that the treatment of perioperative esketamine effectively reduced the occurrence of PPD risk among women who had elective cesarean section. Moreover, esketamine provided improved analgesia on movement postoperatively and decreased the sufentanil uptake after optional cesarean section without significantly raising psychological adverse events. The levels of stress-associated hormone release were significantly reduced by esketamine, and however, no significant changes were noted in biomarkers of PPD. According to the findings of Wang et al. (2022b), the administration of 0.5 mg/kg of a single IV dose of esketamine resulted in a decrease in the occurrence of PPD and EPDS scores at 3-day and 1-month intervals after childbirth [25]. Further research demonstrated that the administration of 0.01 mg/kg/h esketamine infusion for a duration of two days led to a reduced occurrence of PPD and scores of the EPDS on days 3 and 14 following the surgical procedure. However, no significant differences were seen on day 28 post-operation [18]. A new randomized clinical trial suggested that IV infusion of esketamine (0.2 mg/kg) postpartum could decrease the occurrence of PPD in females following cesarean section [26]. Nevertheless, Liu et al. conducted a study in which they investigated the effects of peri-operative administration of esketamine on the incidence of PPD in women who had elective cesarean section. The researchers administered 0.25 mg/kg of esketamine during the intraoperative period and 1.25 mg/kg through PCIA. Their findings indicated that this intervention did not result in a reduction in the risk of PPD in this particular population [16]. Based on the available data, it seems that the observed disparity between our investigation and the prior study [16] may be because of the variation in the dose (1.5 mg/kg in our study) and time (as an adjunct to PCIA in our study) of esketamine. The outcomes of this investigation indicated that post-surgical analgesia with esketamine can exert better analgesic effects on movement status lasting up to 48 h after surgery, but there was no statistical difference in the resting state. The results in the current study are compatible with those in prior investigations [16, 18, 25]. Prior research has shown that the administration of a single IV dose of esketamine or PCIA with the inclusion of esketamine as an adjunct can result in a reduction in the required dosage of analgesics during the first day after a cesarean section procedure [16, 27]. The findings of our investigation indicate that the administration of esketamine by IV infusion as an adjunct to PCIA resulted in a significant decrease in the total amount of sufentanil consumed during the first 24 and 48 h following the surgical procedure. The results presented in our study aligned with previous investigations indicating that varying dosages of esketamine in PCIA after cesarean section resulted in decreased total sufentanil use throughout the first 48 hours after the surgery [25]. In addition, Suppa et al. documented that the intramuscular delivery of esketamine at a dosage of 0.5 mg/kg, accompanied by a continuous infusion at a rate of 2 µg/kg/min for a duration of 12 h, resulted in a reduction in morphine use within the time intervals of 4–8, 8–12, and 12–24 h following a cesarean section procedure [28]. Recent preclinical investigations have provided evidence indicating that the mu-opioid receptor contributes to the pharmacological effects of esketamine [29]. Based on the involvement of esketamine in the opioid system, it suggests the administration of esketamine can have the potential to decrease opioid use among women following elective cesarean delivery. Stress response is a common complication of surgery and anesthesia. It is a normal physiological characteristic, but a strong stress response can stimulate the hypothalamic pituitary adrenal cortex system, leading to an increase in levels of E, NE, and other factors. The results of our study showed the levels of FC, ANP, E, and NE in the esketamine group on day 3 after cesarean section were less than those in the control group, indicating esketamine could effectively alleviate postpartum stress response and reduce body trauma. A systematic review indicated that CRP and IL-6 serve as indicative blood biomarkers for PPD with the presence of inflammation [30]. The occurrence of PPD during a six-month period was shown to be linked to elevated levels of CRP and IL-6 in the blood upon admission [31], indicating that general inflammation is a predictive marker for PPD. Additionally, BDNF lack is a vital factor in perinatal depression [32]. The plasma level of BDNF was shown to be significantly lower in the group of individuals experiencing PPD compared to the group without depressive symptoms six weeks after delivery [33]. However, no significant variations in plasma concentrations of markers (CRP, IL-6, BDNF) were observed between both groups. This finding contradicted the results that esketamine reduced the incidence of PPD at 42 days postoperatively. The possible reason for this is that the levels of markers associated with PPD at 3 days postoperatively do not reflect the risk of mid- and long-term PPD. This investigation has restrictions. Initially, it is important to note that the sample size used in this study was rather small, and the research only focused on Chinese adults from a single location. Therefore, it is necessary to do bigger cohort studies that include many centers and diverse ethnic groups. Second, an esketamine dose of 1.5mg/Kg was utilized in PCIA in our investigation, which is higher than the subanesthetic dose for management of depression [17, 34]; therefore, more assessment is required to determine if the larger or lower dosages are more beneficial and safe in the prevention and treatment of PPD. Third, although PPD often manifests within a month after childbirth [35], and the patients in our study were monitored for a duration of 42 days in order to assess the effects of esketamine, however, the potential long-term consequences of the present action have yet to be determined. Conclusions Our investigation revealed that perioperative injection of esketamine decreased the occurrence of PPD risk in females following elective cesarean section, accompanied by the significant reduction in the concentration of stress-associated hormone release in the esketamine groups. Furthermore, we observed that esketamine decreased the NRS scores on movement and decreased opioid consumption after elective cesarean section without significantly elevating psychological adverse events. However, more large scale randomized, double blind clinical studies need to identify the optimum time/route and dose of esketamine injection to prevent PPD. Abbreviations PPD postpartum depression PCIA patient-controlled intravenous analgesia EPDS Edinburgh postnatal depression scale NRS numerical rating scale NMDAR N-methyl-D-aspartate receptor IV intravenous body mass index BMI FC free cortisol ANP atrial natriuretic peptide E epinephrine NE norepinephrine IL-6 interleukin-6 CRP C-reactive protein BDNF brain-derived neurotrophic factor ANOVA repeated measures analysis of variance Declarations Ethics approval and consent to participate: The research received ethical permission (2022-026) from the Institutional Ethics Committee of the First Hospital of Putian City. Additionally, it was recorded in the Chinese Clinical Trial Registry (ID: ChiCTR2200067054) on 26/12/2022. At recruitment, written informed consent was obtained from each subject. Consent for publication: Prior to the beginning of the trial, everyone who participated in the research gave informed permission. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: Not applicable Authors' contributions: Shurong Li: This author was responsible for patient inclusion and exclusion, preclinical ethics applications and registrations. Zhifang Zhuo: This author performed the clinical data collection and analysis. Renwei Li: This author helped to write and submit our paper. Kaikai Guo: This author helped design this study and conduct our clinical trial. 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Pharmacol Rev 2018, 70 (3):621-660. Zou L, Tian SY, Quan X, Ye TH: [Psychedelic effects of subanesthetic doses of ketamine] . Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2009, 31 (1):68-72. Liu QR, Zong QK, Ding LL, Dai HY, Sun Y, Dong YY, Ren ZY, Hashimoto K, Yang JJ: Effects of perioperative use of esketamine on postpartum depression risk in patients undergoing cesarean section: A randomized controlled trial . J Affect Disord 2023, 339 :815-822. Singh JB, Fedgchin M, Daly E, Xi L, Melman C, De Bruecker G, Tadic A, Sienaert P, Wiegand F, Manji H et al : Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study . Biol Psychiatry 2016, 80 (6):424-431. Han Y, Li P, Miao M, Tao Y, Kang X, Zhang J: S-ketamine as an adjuvant in patient-controlled intravenous analgesia for preventing postpartum depression: a randomized controlled trial . BMC Anesthesiol 2022, 22 (1):49. Wang 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. Gazal M, Motta LS, Wiener CD, Fernandes JC, Quevedo LA, Jansen K, Pinheiro KA, Giovenardi M, Souza DO, Silva RA et al : Brain-derived neurotrophic factor in post-partum depressive mothers . Neurochem Res 2012, 37 (3):583-587. Yang C, Wardenaar KJ, Bosker FJ, Li J, Schoevers RA: Inflammatory markers and treatment outcome in treatment resistant depression: A systematic review . J Affect Disord 2019, 257 :640-649. Cox JL, Holden JM, Sagovsky R: Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale . Br J Psychiatry 1987, 150 :782-786. Lee DT, Yip SK, Chiu HF, Leung TY, Chan KP, Chau IO, Leung HC, Chung TK: Detecting postnatal depression in Chinese women. Validation of the Chinese version of the Edinburgh Postnatal Depression Scale . Br J Psychiatry 1998, 172 :433-437. Xu Y, Li Y, Huang X, Chen D, She B, Ma D: Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective clinical trial . Arch Gynecol Obstet 2017, 295 (5):1167-1174. Wang 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. Wang 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. Behaeen K, Soltanzadeh M, Nesioonpour S, Ebadi A, Olapour A, Aslani SM: Analgesic effect of low dose subcutaneous ketamine administration before and after cesarean section . Iran Red Crescent Med J 2014, 16 (3):e15506. Suppa E, Valente A, Catarci S, Zanfini BA, Draisci G: A study of low-dose S-ketamine infusion as "preventive" pain treatment for cesarean section with spinal anesthesia: benefits and side effects . Minerva Anestesiol 2012, 78 (7):774-781. Levinstein MR, Carlton ML, Di Ianni T, Ventriglia EN, Rizzo A, Gomez JL, Budinich RC, Shaham Y, Airan RD, Zarate CA, Jr. et al : Mu Opioid Receptor Activation Mediates (S)-ketamine Reinforcement in Rats: Implications for Abuse Liability . Biol Psychiatry 2023, 93 (12):1118-1126. Lambert M, Gressier F: [Inflammatory Biomarkers and Postpartum Depression: A Systematic Review of Literature] . Can J Psychiatry 2019, 64 (7):471-481. Liu H, Zhang Y, Gao Y, Zhang Z: Elevated levels of Hs-CRP and IL-6 after delivery are associated with depression during the 6 months post partum . Psychiatry Res 2016, 243 :43-48. Singh S, Fereshetyan K, Shorter S, Paliokha R, Dremencov E, Yenkoyan K, Ovsepian SV: Brain-derived neurotrophic factor (BDNF) in perinatal depression: Side show or pivotal factor? Drug Discov Today 2023, 28 (2):103467. Lee Y, Kim KH, Lee BH, Kim YK: Plasma level of brain-derived neurotrophic factor (BDNF) in patients with postpartum depression . Prog Neuropsychopharmacol Biol Psychiatry 2021, 109 :110245. Salloum NC, Fava M, Hock RS, Freeman MP, Flynn M, Hoeppner B, Cusin C, Iosifescu DV, Trivedi MH, Sanacora G et al : Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression . J Affect Disord 2020, 260 :131-139. Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR: Effects of gonadal steroids in women with a history of postpartum depression . Am J Psychiatry 2000, 157 (6):924-930. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Feb, 2024 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 20 Dec, 2023 Reviews received at journal 19 Dec, 2023 Reviewers agreed at journal 11 Dec, 2023 Reviews received at journal 26 Nov, 2023 Reviewers agreed at journal 24 Nov, 2023 Reviewers agreed at journal 24 Nov, 2023 Reviewers invited by journal 23 Nov, 2023 Editor assigned by journal 23 Nov, 2023 Editor invited by journal 02 Nov, 2023 Submission checks completed at journal 02 Nov, 2023 First submitted to journal 29 Oct, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-3507701","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":245190891,"identity":"63f4d50c-890d-4250-a594-14506557a8d2","order_by":0,"name":"Shurong Li","email":"","orcid":"","institution":"The First Hospital of Putian City","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shurong","middleName":"","lastName":"Li","suffix":""},{"id":245190892,"identity":"0a111f45-26e5-444f-94f1-9591443c7087","order_by":1,"name":"Zhifang Zhuo","email":"","orcid":"","institution":"The First Hospital of Putian City","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhifang","middleName":"","lastName":"Zhuo","suffix":""},{"id":245190895,"identity":"1de51dad-0ff5-4aab-81fa-30901d44ecbd","order_by":2,"name":"Renwei Li","email":"","orcid":"","institution":"The First Hospital of Putian City","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Renwei","middleName":"","lastName":"Li","suffix":""},{"id":245190899,"identity":"5ea407e9-c4d8-4878-bdce-308598200964","order_by":3,"name":"Kaikai Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYJACxg8GEnJs7M0HiFPOA8TMEhUWxnw8xxKI18LAc6YicZ5EjgJxWuz5lz+TkGyTSG9jyGFg+FGxjQhbJB6kSRS2SeS2MZw9wNhz5jYxWg4cA9mS28bYl8DM2EaUloNtErxAh7Ex8xgQqYW/mU2C54xEAhsb0VpusDFbS1RIGLbxsCUcJMov7P3HH978YFAnLz//8cEHPyqI0MIgkcAiAWMfIEI9EPAfYP5AnMpRMApGwSgYsQAAtvI2ezes5M4AAAAASUVORK5CYII=","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kaikai","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2023-10-29 14:59:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3507701/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3507701/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-024-02436-6","type":"published","date":"2024-02-06T15:01:25+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":46024248,"identity":"5f931b97-470e-4406-a898-d6f8053f1ca6","added_by":"auto","created_at":"2023-11-07 17:16:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":677483,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCONSORT flow diagram illustrating the study design and the inclusion/exclusion patient population flow.\u003c/strong\u003e CONSORT Consolidated Standards of Reporting Trials.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3507701/v1/38a1d572ac58c5f2832bdc74.png"},{"id":46024245,"identity":"38c0f4ca-97ae-41ea-9735-2a4a52cb8ac4","added_by":"auto","created_at":"2023-11-07 17:16:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":147687,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe risk of postpartum depression (PPD) and cumulative sufentanil consumption up to 48 hours postoperatively. A\u003c/strong\u003e The Edinburgh Postnatal Depression Scale (EPDS) scores of patients between the control and esketamine groups. \u003cstrong\u003eB\u003c/strong\u003e the incidence of PPD at 42 days after surgery. \u003cstrong\u003eC\u003c/strong\u003ecumulative sufentanil consumption up to 48 h postoperatively. Data were presented as mean ± SD. ****Indicates that the scores on the EPDS were significantly lower in the esketamine group than in the control group (P\u0026lt;0.0001). *Indicates a significant decrease in sufentanil consumption in the esketamine group compared to the control group during 0-24 h, and 0-48 h postoperatively (P\u0026lt;0.05).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3507701/v1/9354a76b8852cf46f053e9cf.png"},{"id":46024247,"identity":"e2262812-6030-42ed-97a0-aa47406ba431","added_by":"auto","created_at":"2023-11-07 17:16:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":752055,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of NRS scores between the control and esketamine groups at rest and during exercise at the same time point. A\u003c/strong\u003e Resting NRS scores between the two groups at 2, 4, 8, 12, 24 and 48 hours postpartum. \u003cstrong\u003eB\u003c/strong\u003e NRS scores during exercise between the two groups at 12, 24 and 48 hours postpartum. *Indicates a significant decrease in NRS scores at rest in the esketamine group compared to the control group (P\u0026lt;0.05). **Indicates P\u0026lt;0.01, ***P\u0026lt;0.001, and ****P\u0026lt;0.0001.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3507701/v1/6a8327ca972c7487033cd1ff.png"},{"id":46024246,"identity":"2db1e5e2-d960-4c43-8d62-78524c224adc","added_by":"auto","created_at":"2023-11-07 17:16:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":435379,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStress hormone expression levels between control and esketamine groups on postoperative day 3.\u003c/strong\u003e \u003cstrong\u003eA\u003c/strong\u003e free cortisol (FC) expression levels between the two groups on postoperative day 3. \u003cstrong\u003eB\u003c/strong\u003ecomparison of the expression levels of atrial natriuretic peptide (ANP) between the two groups on the 3rd post-operative day. \u003cstrong\u003eC\u003c/strong\u003e expression levels of epinephrine (E) between the two groups on postoperative day 3. \u003cstrong\u003eD\u003c/strong\u003eepinephrine (E) expression levels between the two groups on postoperative day 3. ****Indicates a significant decrease in FC, ANP, E and NE in the esketamine group compared to the control group (P\u0026lt;0.0001).\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-3507701/v1/5dcd8cf250603770c5cb3af9.png"},{"id":46024249,"identity":"20955091-3bfa-4259-a716-8b57b5643edc","added_by":"auto","created_at":"2023-11-07 17:16:20","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":191864,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExpression levels of the PPD markers between the control group and the esketamine group on the 3rd post-operative day. A\u003c/strong\u003e expression levels of interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) between the two groups on postoperative day 3. \u003cstrong\u003eB\u003c/strong\u003e C-reactive protein (CRP) expression levels between the two groups on day 3 after surgery.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-3507701/v1/d2c5e0202403a0939e619061.png"},{"id":51006066,"identity":"db402eed-e9ce-4d0a-8eeb-1121551d95fb","added_by":"auto","created_at":"2024-02-12 15:13:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2119819,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3507701/v1/f97fd729-0b02-4878-a221-cf5e3b3ad652.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of esketamine on postpartum depression and pain control after caesarean section: A randomized, double-blind, controlled clinical trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePostpartum depression (PPD) is a prevalent psychological condition seen in females during the perinatal phase, characterized by a frequency ranging from 10\u0026ndash;20%. Notably, the prevalence of PPD tends to be greater in middle and low-income nations [1]. PPD has been seen appear within a range of timeframes after childbirth, including as early as 6 weeks postpartum or later at 3, 6, 12, and even up to 36 months after delivery [2, 3]. Symptoms associated with PPD include feelings of sadness, a persistent state of low mood, diminished appetite, decreased interest in previously enjoyed activities, psychomotor retardation, and disturbances in sleep patterns. Severe PPD has been shown to be associated with an increased risk of suicidal thoughts [4]. PPD has negative effects on both newborns and family connections. Additionally, it places a substantial demand on medical services and resources [5, 6]. The effectiveness of pharmaceutical therapies for PPD is restricted owing to their delayed start of action and poor treatment effectiveness, despite their frequent use [7, 8]. Furthermore, it is worth noting that there are now no pharmacological interventions available for PPD.\u003c/p\u003e \u003cp\u003eKetamine, a dissociative anesthetic, functions as an antagonist of the N-methyl-D-aspartate receptor (NMDAR), which can elicit prompt and enduring antidepressant properties in individuals with depression who have not responded to conventional treatments [9, 10]. The preventive benefits of ketamine against PPD were observed in Chinese women following cesarean section because it decreased PPD when administered intravenously at a dosage of 0.5mg/kg [5]. Nevertheless, the utilization of ketamine in a therapeutic setting as an antidepressant is constrained by its adverse effects, which include dissociative and psychotomimetic manifestations, as well as the potential for addiction [11\u0026ndash;13]. The anesthetic impact of esketamine, a ketamine dextral resolution, has been shown to be twofold more than that of the (R, S)-ketamine mixture and nearly thrice greater than that of (R)-ketamine [14]. Additionally, the incidence of adverse effects associated with esketamine was found to be decreased compared to subanesthetic dosages of ketamine [15].\u003c/p\u003e \u003cp\u003eMultiple clinical investigations have provided evidence supporting the notion that the perioperative intravenous (IV) injection of ketamine has the potential to decrease the occurrence of PPD [16, 17]. The administration of esketamine by IV means at doses of 0.2 and 0.4 mg/kg resulted in prompt and persistent antidepressant impacts in individuals with depression who were unresponsive to conventional treatments [17]. The study conducted by Han et al. (2022) provided evidence supporting the use of esketamine (0.01 mg/kg/h) as an adjuvant in patient-controlled intravenous analgesia (PCIA) to decrease the occurrence of PPD during a two-week period following cesarean section [18]. In addition, Wang and colleagues (2022a) have shown that the administration of esketamine (at doses of 0.1, 0.2, or 0.4 mg/kg) in combination with sufentanil for PCIA resulted in a decrease in the occurrence of PPD, the usage of sufentanil [19]. It seems that the administration of esketamine during the perioperative period may have a preventive effect on the occurrence of PPD after cesarean surgery. However, in a randomized controlled trial, the authors found that the esketamine administration at a dosage of 0.5 mg/kg/h for intraoperative analgesia, as well as esketamine administration at a dosage of 1.25 mg/kg as an adjunct in PCIA, did not result in a reduction in the incidence of PPD risk among women who underwent elective cesarean section [16]. Hence, the existing body of data is deemed inadequate owing to notable variations in the size of the study population, the time and dosage of esketamine administration, and the presence of confounding factors like body mass index (BMI), socioeconomic level, and the specific method of cesarean section.\u003c/p\u003e \u003cp\u003eThe objective of this investigation was to investigate the preventive impact of a higher dose of esketamine infusion (1.5 mg/kg) as a supplementary treatment in PCIA on the risk of PPD in Chinese females following planned cesarean section. The assessment of PPD risk was determined by evaluating screening outcomes, specifically focusing on individuals who obtained an EPDS score of 13 or above. This approach was used instead of relying on prospective formal diagnoses or comprehensive evaluations of medical records. The analgesic effects of esketamine on the parturients after surgery were also explored in our study. Furthermore, we measured the stress hormone levels including free cortisol (FC), atrial natriuretic peptide (ANP), epinephrine (E) and norepinephrine (NE), and PPD biomarkers (e.g. interleukin-6 [IL-6], C-reactive protein [CRP], and brain-derived neurotrophic factor [BDNF]) in the blood since these markers are revealed to have a function in PPD and antidepressant impact of ketamine [20, 21].\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe present study was a prospective, double-blind, randomized controlled experiment that took place at the First Hospital of Putian City in China from September 2022 to July 2023. The annual number of births is around 2000, with cesarean deliveries accounting for 600 of these cases. The research received ethical permission (2022-026) from the Institutional Ethics Committee of the First Hospital of Putian City. Additionally, it was recorded in the Chinese Clinical Trial Registry (ID: ChiCTR2200067054) on 26/12/2022. Prior to the beginning of the trial, everyone who participated in the research gave informed permission.\u003c/p\u003e \u003cp\u003eA total of 246 maternity women who were classified as American Society of Anesthesiologists physical status II, aged between 19 and 44 years, and having elective surgical operations under general anesthesia were included in the investigation. The criteria for exclusion were as follows: (1) mental disorder; (2) serious obstetric problems or underlying medical conditions; (3) esketamine allergy; and (4) ineligibility for intraspinal anesthesia.\u003c/p\u003e \u003cp\u003eIn accordance with the findings obtained from our preliminary experiment, which had a sample size of 20 individuals in each group, the pre-test data indicated that the prevalence of PPD was 24% in the placebo group and 10% in the esketamine group. The sample size needed for each group was determined to be 110 individuals, based on a power of 80% and a significance level of 5%. This calculation was performed employing the PASS 15.0 program developed by Stata Corp. LP, located in College Station, TX, USA. In order to account for an expected participant dropout rate of 10%, it was determined that each arm of the study would have 120 individuals. The flow chart of the research participants' recruitment is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, illustrating the Consolidated Standards of Reporting Trials.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe subjects were randomized to two groups, namely the esketamine and the control groups, in a random manner, with an equal number of participants in each group. The esketamine group received esketamine, while the control group received normal saline. The process of simple randomization was performed utilizing IBM SPSS program version 26.0 (SPSS Inc., Chicago, IL, USA). This program produced random numbers to allocate participants to different groups. The pharmacist made syringes filled with esketamine or a solution of normal saline. The aforementioned items were enclosed into envelopes that were numbered in consecutive order and afterwards transported to the designated operation room. The nurse sequentially opened the envelopes in accordance with their numbered order. Every individual envelope was found to contain a syringe. The randomization assignment was concealed from both the participants and investigators in order to maintain blinding.\u003c/p\u003e \u003cp\u003eAll females who experienced delivery had spinal anesthetic at the L3-L4 or L2-L3 and subjected to PCIA after operation. The administration of the anesthetic solution, consisting of 2 mL of 1% ropivacaine and 1 mL of 10% glucose, was performed by a qualified anesthesiologist. The dosage provided was 1 mL every 5 s, with the aim of attaining the maximum degree of sensory block at the T4-T6. Following the completion of the surgical procedure, all patients were given non-steroidal anti-inflammatory medicines in the form of a 40 mg IV dose of flurbiprofen. Additionally, preemptive analgesia was provided utilizing ultrasound-guided transversus abdominis plane block. The control group in the study included a combination of 2 \u0026micro;g/kg sufentanil and 10 mg tropisetron. On the other hand, the esketamine group received a combination of 2 \u0026micro;g/kg sufentanil, 10 mg tropisetron, and esketamine at a dosage of 1.5 mg/kg. These combinations were administered in a total volume of 100 mL. All participants were administered a continuous infusion at a baseline rate of 2 mL/h, as well as a 1 mL on-demand bolus with a 15 min lockout interval. The administration of the infusion initiated instantly after the closure of the skin incision and continued for two days. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire was administered to the subjects in a face-to-face interview conducted the day before to surgical preparation. The participants were contacted by telephone or WeChat in order to finish EPDS 42 days post-cesarean section, with the aim of diagnosing PPD. EPDS, a diagnostic instrument used for detecting PPD cases [22], has undergone translation into the Chinese language to facilitate the assessment of Chinese patients [23]. The EPDS comprises a set of 10 questions, with each item carrying a maximum score of three points. Consequently, the cumulative score attainable on the EPDS equals 30 points. In the present investigation, we classified EPDS scores equal to or more than 13 as indicative of postpartum depression [24].\u003c/p\u003e \u003cp\u003eThe main objective of the research was to assess the occurrence of PPD risk 42 days after childbirth. This was accomplished by employing the EPDS administered by means of a web-based questionnaire. The secondary outcomes assessed in the study included cumulative sufentanil consumption, postoperative pain intensity, plasma levels of stress hormone levels and PPD biomarkers, and incidence of adverse events. The total amount of sufentanil consumed throughout certain time periods after the surgical procedure, including the intervals of 0\u0026ndash;24 h, 24\u0026ndash;48 h, and 0\u0026ndash;48 h. Pain severity was evaluated utilizing the numeric rating scale (NRS) score, with pain scores at rest and throughout movements documented at 2, 4, 8, 12, 24, and 48 h after cesarean delivery. The enzyme-linked immunosorbent assay was employed to detect the plasma levels of FC, ANP, E, NE, CRP, IL-6, and BDNF on the day prior to preparation of surgery and on day 3 after surgery. The blood samples were obtained between the time frame of 6 to 7 a.m. Negative side effects throughout PCIA, like headache, nausea, vomiting, dizziness, drowsiness, and itching were reported. Demographic features, like weight, height, calculated BMI, age, gestational weeks, pregnancy complications, gravidity, parity, marital status, educational level, and EPDS scores, were obtained the day prior to the operation.\u003c/p\u003e \u003cp\u003eSPSS IBM statistical program package, version 26.0 (SPSS Inc., Chicago, IL), was employed to conduct Data analysis. Shapiro-Wilk test was utilized to detect the Normality assumptions for continuous variables. The independent sample t-test or Mann-Whitney U test were employed to test the between-group variations for continuous normally distributed variables or non-normally distributed variables, respectively. The chi-square test was employed to compare categorical variables between groups. The NRS score was quantified employing the mean and standard deviation, and the variations between groups were assessed by repeated measures analysis of variance (ANOVA), and multiple comparisons were analyzed by Bonferroni adjustment. The observed results were deemed to be statistically significant, as shown by a p-value of less than 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTypically, 360 parturients were enrolled between January 1, 2023, and September 31, 2023. Of these, 36 refused to receive PCIA after cesarean delivery, 12 underwent combined spinal-epidural anesthesia and general anesthesia, 16 experienced life-threatening chronic comorbid diseases, 21 participated in other clinical studies, and 275 participants were randomized into the esketamine and the control groups. Twenty-nine parturients were lost to follow-up. Consequently, the study included a total of 246 cases (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e provides a comprehensive overview of the demographic and clinical features of the patients. No statistically significant variations were observed 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\u003ePreoperative data of the included pregnant women\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=\"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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\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\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEsketamine group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u0026ndash;42\u003c/p\u003e \u003cp\u003e27.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u0026ndash;44\u003c/p\u003e \u003cp\u003e28\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pregnancy BMI (kg/m2), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52\u0026ndash;77\u003c/p\u003e \u003cp\u003e24.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u0026ndash;75\u003c/p\u003e \u003cp\u003e24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational weeks, n (%)\u003c/p\u003e \u003cp\u003eFull term\u003c/p\u003e \u003cp\u003ePreterm\u003c/p\u003e \u003cp\u003ePost term\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101 (82.77)\u003c/p\u003e \u003cp\u003e14 (11.48)\u003c/p\u003e \u003cp\u003e7 (5.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106 (85.48)\u003c/p\u003e \u003cp\u003e12 (9.67)\u003c/p\u003e \u003cp\u003e6 (4.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy complications, n (%)\u003c/p\u003e \u003cp\u003eGestational diabetes\u003c/p\u003e \u003cp\u003eGestational hypertension\u003c/p\u003e \u003cp\u003eGestational Low thyroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (10.66)\u003c/p\u003e \u003cp\u003e21 (17.21)\u003c/p\u003e \u003cp\u003e32 (26.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (9.68)\u003c/p\u003e \u003cp\u003e24 (19.35)\u003c/p\u003e \u003cp\u003e35 (28.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003cp\u003e0.74\u003c/p\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravidity, n (%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e\u0026ge;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (38.52)\u003c/p\u003e \u003cp\u003e75 (61.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (40.32)\u003c/p\u003e \u003cp\u003e74 (59.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity, n (%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e\u0026ge;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (50)\u003c/p\u003e \u003cp\u003e61 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (52.42)\u003c/p\u003e \u003cp\u003e59 (47.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarital status, n (%)\u003c/p\u003e \u003cp\u003eMarried\u003c/p\u003e \u003cp\u003eDivorced\u003c/p\u003e \u003cp\u003eUnmarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e121 (99.18)\u003c/p\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003cp\u003e1 (0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e122 (98.39)\u003c/p\u003e \u003cp\u003e1 (0.81)\u003c/p\u003e \u003cp\u003e1 (0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducational level, n (%)\u003c/p\u003e \u003cp\u003eMaster or above\u003c/p\u003e \u003cp\u003eBachelor or below\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (35.25)\u003c/p\u003e \u003cp\u003e79 (64.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (40.32)\u003c/p\u003e \u003cp\u003e74 (59.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStress hormone levels, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFree cortisol (FC) (nmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e261.51\u0026thinsp;\u0026plusmn;\u0026thinsp;55.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e251.98\u0026thinsp;\u0026plusmn;\u0026thinsp;62.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial natriuretic peptide (ANP) (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpinephrine (E) (ng/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.09\u0026thinsp;\u0026plusmn;\u0026thinsp;4.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.92\u0026thinsp;\u0026plusmn;\u0026thinsp;5.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNorepinephrine (NE) (ng/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159.82\u0026thinsp;\u0026plusmn;\u0026thinsp;32.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e155.16\u0026thinsp;\u0026plusmn;\u0026thinsp;43.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiomarkers, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein (CRP) (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterleukin-6 (IL-6) (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrain-derived neurotrophic factor (BDNF) (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEdinburgh Postpartum Depression Scale, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe rate of depression was significantly lower in the esketamine group in contrast to that in the control group at 42 days after cesarean section (22.2% and 10.7%, P\u0026thinsp;=\u0026thinsp;0.015) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The scores of EPDS were comparable between the esketamine and control groups before operation (3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0 vs. 4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1, P\u0026thinsp;=\u0026thinsp;0.23). Nevertheless, significant inter-group variations in scores of EPDS were detected at 42 days postpartum (6.87\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14 vs. 9.02\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe consumption of sufentanil throughout the first day (42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.58 \u0026micro;g vs 50.15\u0026thinsp;\u0026plusmn;\u0026thinsp;5.47 \u0026micro;g, P\u0026thinsp;=\u0026thinsp;0.04) and two days (87.40\u0026thinsp;\u0026plusmn;\u0026thinsp;9.51 \u0026micro;g vs 95.10\u0026thinsp;\u0026plusmn;\u0026thinsp;9.36 \u0026micro;g, P\u0026thinsp;=\u0026thinsp;0.04) after surgery were significantly lower in the esketamine group than that in the control group. Nevertheless, there was no statistically significant variation observed during the 24\u0026ndash;48 h postpartum period (43.50\u0026thinsp;\u0026plusmn;\u0026thinsp;5.34 \u0026micro;g vs 46.40\u0026thinsp;\u0026plusmn;\u0026thinsp;3.86 \u0026micro;g, P\u0026thinsp;=\u0026thinsp;0.71) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). NRS scores at rest were unchanged in the esketamine group at 2, 4, 8, 12, 24, 48 h after cesarean section (1.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65 vs 1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56, P\u0026thinsp;=\u0026thinsp;0.49; 4.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94 vs 4.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88, P\u0026thinsp;=\u0026thinsp;0.20; 3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53 vs 3.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64, P\u0026thinsp;=\u0026thinsp;0.88; 2.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64 vs 3.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73, P\u0026thinsp;=\u0026thinsp;0.57; 2.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 vs 3.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75, P\u0026thinsp;=\u0026thinsp;0.40; 1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62 vs 2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43, P\u0026thinsp;=\u0026thinsp;0.20, respectively). Contrarily, significant variations on movement were observed between both groups at 24, 48 h after cesarean section (3.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57 vs 4.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80, P\u0026thinsp;=\u0026thinsp;0.02; 2.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87 vs 3.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76, P\u0026thinsp;=\u0026thinsp;0.02), rather than at 12 h (4.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86 vs 5.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95, P\u0026thinsp;=\u0026thinsp;0.06) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSerum FC and ANP levels were substantially lesser in esketamine group than that in the control group (FC: 302\u0026thinsp;\u0026plusmn;\u0026thinsp;101 vs 382\u0026thinsp;\u0026plusmn;\u0026thinsp;91 nmol/L, P˂0.0001; ANP: 0.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23 vs 1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42 ng/mL, P˂0.0001), and the E and NE level was significantly decreased in esketamine group in contrast to that in the control group (E: 39.47\u0026thinsp;\u0026plusmn;\u0026thinsp;4.58 vs 54.32\u0026thinsp;\u0026plusmn;\u0026thinsp;6.19 ng/L, P˂0.0001; NE: 160.84\u0026thinsp;\u0026plusmn;\u0026thinsp;39.45 vs 190.31\u0026thinsp;\u0026plusmn;\u0026thinsp;43.29 ng/L, P˂0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). There was no statistically significant difference seen in the plasma concentrations of CRP and IL-6 between both groups on the third day following the surgical procedure (CRP: 1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32 vs 1.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29 mg/ml, P\u0026thinsp;=\u0026thinsp;0.31; IL-6: 8.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12 vs 7.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91 pg/mL, P\u0026thinsp;=\u0026thinsp;0.49, respectively). Likewise, there were no statistically significant variations observed in the plasma concentrations of BDNF among both groups (1.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62 vs 1.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44 pg/mL, P\u0026thinsp;=\u0026thinsp;0.06) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe predominant side effects seen in the placebo group during the surgical procedure were nausea and vomiting (27.42%), dizziness (16.94%), pruritus (8.84%), and drowsiness (2.41%). Esketamine group were nausea and vomiting (25.41%), dizziness (22.95%), pruritus (6.56%), and drowsiness (0.82%). There were no statistically significant variations observed in the occurrence of adverse events between both groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05, 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\u003eAnalgesia-related adverse events, n (%)\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=\".\" 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 \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\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEsketamine group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea and vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31(25.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34(27.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDizziness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28(22.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21(16.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8(6.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6(8.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrowsiness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1(0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3(2.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings of this randomized controlled investigation indicate that the treatment of perioperative esketamine effectively reduced the occurrence of PPD risk among women who had elective cesarean section. Moreover, esketamine provided improved analgesia on movement postoperatively and decreased the sufentanil uptake after optional cesarean section without significantly raising psychological adverse events. The levels of stress-associated hormone release were significantly reduced by esketamine, and however, no significant changes were noted in biomarkers of PPD.\u003c/p\u003e \u003cp\u003eAccording to the findings of Wang et al. (2022b), the administration of 0.5 mg/kg of a single IV dose of esketamine resulted in a decrease in the occurrence of PPD and EPDS scores at 3-day and 1-month intervals after childbirth [25]. Further research demonstrated that the administration of 0.01 mg/kg/h esketamine infusion for a duration of two days led to a reduced occurrence of PPD and scores of the EPDS on days 3 and 14 following the surgical procedure. However, no significant differences were seen on day 28 post-operation [18]. A new randomized clinical trial suggested that IV infusion of esketamine (0.2 mg/kg) postpartum could decrease the occurrence of PPD in females following cesarean section [26]. Nevertheless, Liu et al. conducted a study in which they investigated the effects of peri-operative administration of esketamine on the incidence of PPD in women who had elective cesarean section. The researchers administered 0.25 mg/kg of esketamine during the intraoperative period and 1.25 mg/kg through PCIA. Their findings indicated that this intervention did not result in a reduction in the risk of PPD in this particular population [16]. Based on the available data, it seems that the observed disparity between our investigation and the prior study [16] may be because of the variation in the dose (1.5 mg/kg in our study) and time (as an adjunct to PCIA in our study) of esketamine.\u003c/p\u003e \u003cp\u003eThe outcomes of this investigation indicated that post-surgical analgesia with esketamine can exert better analgesic effects on movement status lasting up to 48 h after surgery, but there was no statistical difference in the resting state. The results in the current study are compatible with those in prior investigations [16, 18, 25]. Prior research has shown that the administration of a single IV dose of esketamine or PCIA with the inclusion of esketamine as an adjunct can result in a reduction in the required dosage of analgesics during the first day after a cesarean section procedure [16, 27]. The findings of our investigation indicate that the administration of esketamine by IV infusion as an adjunct to PCIA resulted in a significant decrease in the total amount of sufentanil consumed during the first 24 and 48 h following the surgical procedure. The results presented in our study aligned with previous investigations indicating that varying dosages of esketamine in PCIA after cesarean section resulted in decreased total sufentanil use throughout the first 48 hours after the surgery [25]. In addition, Suppa et al. documented that the intramuscular delivery of esketamine at a dosage of 0.5 mg/kg, accompanied by a continuous infusion at a rate of 2 \u0026micro;g/kg/min for a duration of 12 h, resulted in a reduction in morphine use within the time intervals of 4\u0026ndash;8, 8\u0026ndash;12, and 12\u0026ndash;24 h following a cesarean section procedure [28]. Recent preclinical investigations have provided evidence indicating that the mu-opioid receptor contributes to the pharmacological effects of esketamine [29]. Based on the involvement of esketamine in the opioid system, it suggests the administration of esketamine can have the potential to decrease opioid use among women following elective cesarean delivery.\u003c/p\u003e \u003cp\u003eStress response is a common complication of surgery and anesthesia. It is a normal physiological characteristic, but a strong stress response can stimulate the hypothalamic pituitary adrenal cortex system, leading to an increase in levels of E, NE, and other factors. The results of our study showed the levels of FC, ANP, E, and NE in the esketamine group on day 3 after cesarean section were less than those in the control group, indicating esketamine could effectively alleviate postpartum stress response and reduce body trauma. A systematic review indicated that CRP and IL-6 serve as indicative blood biomarkers for PPD with the presence of inflammation [30]. The occurrence of PPD during a six-month period was shown to be linked to elevated levels of CRP and IL-6 in the blood upon admission [31], indicating that general inflammation is a predictive marker for PPD. Additionally, BDNF lack is a vital factor in perinatal depression [32]. The plasma level of BDNF was shown to be significantly lower in the group of individuals experiencing PPD compared to the group without depressive symptoms six weeks after delivery [33]. However, no significant variations in plasma concentrations of markers (CRP, IL-6, BDNF) were observed between both groups. This finding contradicted the results that esketamine reduced the incidence of PPD at 42 days postoperatively. The possible reason for this is that the levels of markers associated with PPD at 3 days postoperatively do not reflect the risk of mid- and long-term PPD.\u003c/p\u003e \u003cp\u003eThis investigation has restrictions. Initially, it is important to note that the sample size used in this study was rather small, and the research only focused on Chinese adults from a single location. Therefore, it is necessary to do bigger cohort studies that include many centers and diverse ethnic groups. Second, an esketamine dose of 1.5mg/Kg was utilized in PCIA in our investigation, which is higher than the subanesthetic dose for management of depression [17, 34]; therefore, more assessment is required to determine if the larger or lower dosages are more beneficial and safe in the prevention and treatment of PPD. Third, although PPD often manifests within a month after childbirth [35], and the patients in our study were monitored for a duration of 42 days in order to assess the effects of esketamine, however, the potential long-term consequences of the present action have yet to be determined.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur investigation revealed that perioperative injection of esketamine decreased the occurrence of PPD risk in females following elective cesarean section, accompanied by the significant reduction in the concentration of stress-associated hormone release in the esketamine groups. Furthermore, we observed that esketamine decreased the NRS scores on movement and decreased opioid consumption after elective cesarean section without significantly elevating psychological adverse events. However, more large scale randomized, double blind clinical studies need to identify the optimum time/route and dose of esketamine injection to prevent PPD.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePPD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epostpartum depression\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCIA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epatient-controlled intravenous analgesia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEPDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEdinburgh postnatal depression scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNRS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enumerical rating scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNMDAR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eN-methyl-D-aspartate receptor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintravenous\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ebody mass index\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efree cortisol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eatrial natriuretic peptide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eepinephrine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enorepinephrine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-6\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterleukin-6\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBDNF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebrain-derived neurotrophic factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANOVA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erepeated measures analysis of variance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe research received ethical permission (2022-026) from the Institutional Ethics Committee of the First Hospital of Putian City. Additionally, it was recorded in the Chinese Clinical Trial Registry (ID: ChiCTR2200067054) on 26/12/2022. At recruitment, written informed consent was obtained from each subject.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003ePrior to the beginning of the trial, everyone who participated in the research gave informed permission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e \u003cstrong\u003eShurong Li:\u003c/strong\u003e This author was responsible for patient inclusion and exclusion, preclinical ethics applications and registrations. \u003cstrong\u003eZhifang Zhuo:\u003c/strong\u003e This author performed the clinical data collection and analysis. \u003cstrong\u003eRenwei Li:\u0026nbsp;\u003c/strong\u003eThis author helped to write and submit our paper. \u003cstrong\u003eKaikai Guo:\u003c/strong\u003e This author helped design this study and conduct our clinical trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e Not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBeneyto M, Meador-Woodruff JH: \u003cstrong\u003eLamina-specific abnormalities of NMDA receptor-associated postsynaptic protein transcripts in the prefrontal cortex in schizophrenia and bipolar disorder\u003c/strong\u003e. \u003cem\u003eNeuropsychopharmacology \u003c/em\u003e2008, \u003cstrong\u003e33\u003c/strong\u003e(9):2175-2186.\u003c/li\u003e\n\u003cli\u003eWisner KL, Moses-Kolko EL, Sit DK: \u003cstrong\u003ePostpartum depression: a 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Esketamine's effects on PPD in women undergoing cesarean section remain contradictory, despite ketamine's prophylactic effects. This study evaluated the effect of esketamine as an adjunct to patient-controlled intravenous analgesia (PCIA) to prevent PPD in women undergoing caesarean section.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 275 parturients scheduled for caesarean section and subsequent PCIA were recruited from a single centre and randomised to control (sufentanil 2 \u0026micro;g/kg\u0026thinsp;+\u0026thinsp;tropisetron 10 mg) or esketamine (additional esketamine 1.5 mg/kg). The primary outcome was the incidence of PPD, as measured by the Edinburgh postnatal depression scale (EPDS), following surgery. Secondary outcomes were cumulative sufentanil consumption, numerical rating scale (NRS) scores, stress hormone levels and biomarkers of PPD.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 246 postpartum women with caesarean delivery were included in the final analysis. The incidence of depression among parturients on postoperative day 42 was higher in the control group compared to the esketamine group, with rates of 17.6% and 8.2% respectively (P\u0026thinsp;=\u0026thinsp;0.02). The EPDS scores were significantly higher in the control group, with a mean score of 9.02\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21 vs. 6.87\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14 in the esketamine group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Sufentanil consumption was significantly lower in the esketamine group in the 0\u0026ndash;24 h (42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.58 \u0026micro;g vs 50.15\u0026thinsp;\u0026plusmn;\u0026thinsp;5.47 \u0026micro;g, P\u0026thinsp;=\u0026thinsp;0.04) and 0\u0026ndash;48 h (87.40\u0026thinsp;\u0026plusmn;\u0026thinsp;9.51 \u0026micro;g vs 95.10\u0026thinsp;\u0026plusmn;\u0026thinsp;9.36 \u0026micro;g, P\u0026thinsp;=\u0026thinsp;0.04) postoperative periods compared to the control group. Significant differences in movement were observed between the two groups at 24 and 48 hours after cesarean section (3.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57 vs 4.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80, P\u0026thinsp;=\u0026thinsp;0.02; 2.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87 vs 3.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76, P\u0026thinsp;=\u0026thinsp;0.02). Furthermore, the plasma level of stress hormone was significantly lower on postoperative day 3 in the esketamine group compared to the control group. The frequency of side effects observed in both groups was comparable.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eEsketamine (1.5 mg/kg) used as a supplement in PCIA significantly decreases the occurrence of PPD in 42 days and reduced cumulative sufentanil consumption in a span of 48 hours post-cesarean operation, without raising the rate of adverse effects.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eRegistered in the Chinese Clinical Trial Registry (ChiCTR2200067054) on December 26, 2022.\u003c/p\u003e","manuscriptTitle":"Effect of esketamine on postpartum depression and pain control after caesarean section: A randomized, double-blind, controlled clinical trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-07 17:16:15","doi":"10.21203/rs.3.rs-3507701/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2023-12-20T09:46:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-12-19T20:57:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"dded48d5-163c-4c31-ab59-afa62ec9277f","date":"2023-12-11T06:22:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-11-26T19:52:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0dcaa2d6-2b09-4add-8fb9-7668a0005312","date":"2023-11-24T08:17:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"1aacab20-5c9c-4e44-808d-7687a81bf3af_SNPRID","date":"2023-11-24T05:04:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-11-24T03:51:23+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-11-23T12:34:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-11-02T11:17:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-11-02T11:16:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2023-10-29T14:54:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b77d63d9-e509-4be0-baef-11622d3443ad","owner":[],"postedDate":"November 7th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-02-12T15:11:49+00:00","versionOfRecord":{"articleIdentity":"rs-3507701","link":"https://doi.org/10.1186/s12871-024-02436-6","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2024-02-06 15:01:25","publishedOnDateReadable":"February 6th, 2024"},"versionCreatedAt":"2023-11-07 17:16:15","video":"","vorDoi":"10.1186/s12871-024-02436-6","vorDoiUrl":"https://doi.org/10.1186/s12871-024-02436-6","workflowStages":[]},"version":"v1","identity":"rs-3507701","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3507701","identity":"rs-3507701","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}