Abstract
This study aims to evaluate the clinical efficacy and safety of esketamine for postoperative analgesia in women undergoing cesarean section and explore its effects on mood (anxiety and depression) and sleep quality during the recovery period. This retrospective cohort study included 125 full-term pregnant women who underwent cesarean delivery at our hospital between January 2023 and June 2024. Based on the type of postoperative analgesia administered, patients were allocated to either an esketamine group (n = 64) or a conventional analgesia group (n = 61). Pain intensity (measured via Visual Analog Scale [VAS] scores at 4, 12, 24, and 48 hours post-surgery), mood indicators (anxiety and depression scores on postoperative days 3, 7, and 28), sleep quality (assessed using the Pittsburgh Sleep Quality Index), and the incidence of adverse events were recorded and analyzed. Patients receiving esketamine reported significantly lower VAS pain scores at all postoperative time points compared to those in the control group. Specifically, at 12 hours post-surgery, the resting VAS score was 2.13 ± 0.38 in the esketamine group versus 2.53 ± 0.51 in the control group (P < .001); at 24 hours, it was 1.78 ± 0.27 versus 2.01 ± 0.29 (P < .001), and at 48 hours, it was 1.41 ± 0.39 versus 1.72 ± 0.37 (P < .001). Anxiety and depression scores were consistently reduced in the esketamine group at all assessed time intervals (e.g., Edinburgh Postnatal Depression Scale score at 3 days: 8.95 ± 1.47 in the esketamine group versus 11.37 ± 2.71 in the control group, P < .001). Sleep quality, as reflected by Pittsburgh Sleep Quality Index scores, was significantly better in the esketamine group at 3 days (11.25 ± 1.07 vs 12.41 ± 2.43, P = .002), 1 week (10.13 ± 1.73 vs 11.53 ± 1.37, P < .001), and 4 weeks (9.78 ± 1.28 vs 10.51 ± 1.55, P = .011). No significant differences were observed between the 2 groups regarding adverse events, and no serious complications were noted in either group. Esketamine demonstrates superior efficacy in managing postoperative pain, alleviating anxiety and depression, and improving sleep quality after cesarean section, with no increase in adverse effects. These findings suggest that esketamine may serve as a valuable option for enhancing postoperative recovery in cesarean patients.
Keywords: anxiety, cesarean section, depression, esketamine, postoperative analgesia, sleep quality
1. Introduction
Cesarean section is a commonly performed obstetric surgery, widely used to address maternal or fetal crises during the labor process.[1,2] Although the safety and success rates of cesarean section have steadily improved, postoperative pain management remains a critical issue in the recovery of parturients.[3,4] Unmanaged postoperative pain not only affects maternal comfort but can also lead to various negative consequences, including disrupted sleep, impaired early mobilization, and gastrointestinal dysfunction, all of which contribute to prolonged recovery and extended hospital stays.[5] Moreover, inadequately controlled pain can lead to psychological disturbances such as anxiety and depression, which may affect mother–infant bonding and breastfeeding behaviors, further hindering postpartum recovery.[6,7] Consequently, identifying more effective analgesic methods with fewer side effects has become an urgent focus in contemporary medical research.
Current postoperative analgesia strategies for cesarean section include opioid analgesics, nonsteroidal anti-inflammatory drugs, and local anesthetics.[8,9] Despite their widespread use, these traditional analgesics have notable limitations. Opioids, while potent analgesics, are associated with side effects such as nausea, vomiting, drowsiness, and respiratory depression, which pose significant safety risks to parturients. Nonsteroidal anti-inflammatory drugs, although effective in reducing pain, may increase the risk of postoperative bleeding, and local anesthetics, while commonly used, have limited efficacy, with their analgesic effects diminishing over time.[10,11] These limitations highlight the need for an analgesic agent that provides effective pain relief while minimizing adverse effects.
Esketamine, the S-enantiomer of ketamine, has emerged as a promising alternative for pain management in clinical settings.[12] Compared to traditional ketamine, esketamine has stronger analgesic properties and produces fewer central nervous system side effects, making it an attractive option for postoperative pain relief.[13,14] Recent studies have increasingly focused on the analgesic effects of esketamine in various surgical contexts, particularly following cesarean section.[15] Clinical evidence suggests that esketamine not only alleviates postoperative pain effectively but also reduces opioid consumption and demonstrates superior clinical operability due to its minimal side effects.[16] However, the role of esketamine in postoperative analgesia following cesarean section has not been fully explored, especially regarding its impact on maternal psychological outcomes such as anxiety and depression.
Postoperative anxiety and depression are common psychological issues in women undergoing cesarean section.[17] Research indicates that the incidence of these conditions is significantly higher in parturients following cesarean section, and these emotional disturbances are closely linked to slower recovery and poorer overall health outcomes.[18,19] Postoperative anxiety and depression not only negatively affect maternal emotional well-being and quality of life but also hinder the establishment of mother–infant bonding and can adversely affect infant health.[20,21] Studies have demonstrated that inadequate pain control is a significant contributor to the development of anxiety and depression in postpartum women.[22] Furthermore, recent research has highlighted the importance of addressing both physical pain and emotional well-being in postoperative care. For example, a study by Smith et al found that integrating psychological support and effective pain management significantly improved recovery outcomes and maternal mental health following cesarean sections.[22] As a result, improving maternal mental health through pharmacological interventions has garnered increasing attention in recent years. Given its analgesic properties and effects on the central nervous system, esketamine may offer dual benefits by alleviating postoperative pain and improving anxiety and depressive symptoms. However, research in this area remains in its early stages.[23]
Several studies have shown the positive effects of esketamine in other surgical contexts, but research specifically focusing on its impact in cesarean section recovery is limited. For example, Jones et al[23] demonstrated that esketamine significantly reduced opioid consumption in patients undergoing major abdominal surgeries. Furthermore, its effects on sleep disturbances and mood disorders in postoperative patients have been explored in some studies, but these effects have not been well documented in cesarean section patients. Recent research also suggests that addressing psychological factors such as anxiety and depression in the postpartum period can improve maternal outcomes and facilitate quicker recovery, making esketamine a potentially invaluable treatment option. Addressing this gap, the present study aims to evaluate the effectiveness of esketamine in managing postoperative pain following cesarean section and to explore its potential impact on maternal anxiety and depression. The novelty of this study lies in its comprehensive approach, which not only focuses on pain relief but also assesses the multidimensional effects of esketamine on maternal psychological health, particularly its potential to enhance postpartum recovery. By comparing the outcomes of esketamine with those of traditional analgesic regimens in terms of pain management, anxiety, depression, and other relevant factors, we aim to provide more scientifically grounded and clinically applicable strategies for pain management and psychological intervention, ultimately optimizing the overall treatment plan for cesarean section patients.
2. Methods
2.1. Study design
This study was approved by the Ethics Committee of Jiangxi Provincial Maternal and Child Health Hospital. This study utilized a retrospective cohort design to assess the efficacy of esketamine in postoperative pain management following cesarean section. Additionally, it aimed to examine the impact of esketamine on postoperative anxiety and depression in parturients. The study was approved by the hospital’s ethics committee and adhered to all privacy protection regulations. Patient data were anonymized and de-identified to ensure confidentiality, with data exclusively used for academic purposes and publication. Informed consent was obtained from all participants, and all procedures were conducted according to ethical guidelines.
2.2. Study participants
This retrospective cohort study included 125 full-term pregnant women who underwent cesarean delivery at our hospital between January 2023 and June 2024. Patients were allocated to either the esketamine group (n = 64) or the conventional analgesia group (n = 61) based on the type of postoperative analgesia administered. To minimize confounding effects, we performed multivariate adjustment for key baseline characteristics, such as age, body mass index (BMI), gestational age, and the American Society of Anesthesiologists (ASA) Physical Status , ensuring that the groups were comparable. The inclusion and exclusion criteria were carefully designed to further minimize potential bias by ensuring that participants in both groups had no significant preexisting comorbidities or psychiatric conditions.
Inclusion criteria: The study included pregnant women aged 20 to 39 years who had a singleton, term pregnancy and were classified as ASA physical status I or II. Participants had a BMI < 35 kg/m² and no significant comorbidities or obstetric complications. All participants underwent spinal–epidural combined anesthesia during surgery and received postoperative pain management. Additionally, eligible participants had complete medical records, including preoperative assessment, intraoperative anesthesia records, and postoperative analgesia data. Informed consent was obtained, and the participants were willing to complete follow-up psychological assessments, such as anxiety and depression scales.
Exclusion criteria: Exclusion from the study occurred for individuals with incomplete medical records or missing postoperative analgesia or anxiety/depression assessment data. Women with preexisting psychiatric conditions, such as anxiety or depression, were also excluded. Other exclusion factors included significant intraoperative or postoperative complications (e.g., major hemorrhage ≥ 1500 mL, uterine rupture, or placental abruption), as well as allergies to ketamine or esketamine, substance abuse, or a history of chronic alcoholism. Participants with uncontrolled hypertension (systolic BP ≥ 160 mm Hg or diastolic BP ≥ 100 mm Hg), severe cardiovascular diseases, or other medical conditions that contraindicated study participation were also excluded. Additionally, women who required transfer to the ICU or specialized nursing care postoperatively, or who had severe metabolic disorders, liver, or kidney dysfunction, were not eligible.
2.3. Anesthesia and postoperative analgesia regimen
2.3.1. Anesthesia procedure
Upon arrival in the operating room, standard monitoring was initiated, including noninvasive blood pressure, oxygen saturation, and electrocardiogram. Intravenous access was established, and appropriate fluid resuscitation was administered. The patient was positioned in the left lateral decubitus position with a flexed knee to facilitate spinal–epidural anesthesia. After local skin anesthesia with 1% lidocaine, the epidural needle was inserted at the L2 to 3 or L3 to 4 intervertebral space. Once the epidural space was identified via loss of resistance, a spinal needle was advanced into the subarachnoid space, with clear cerebrospinal fluid return confirming correct placement. A dose of 0.75% ropivacaine (1.8–2.0 mL) was injected intrathecally, followed by insertion of an epidural catheter 3 to 5 cm into the epidural space.
After catheter fixation, the patient was repositioned in the supine position with a 15 to 30° left tilt to reduce the risk of hypotension. Anesthesia was maintained at the T6 to T8 level with supplemental doses of local anesthetics as needed. Fluids and vasoactive agents were administered to maintain hemodynamic stability. At the end of surgery, dexamethasone (5 mg) was administered intravenously for nausea prevention, and 1 mg of butorphanol was given for pain relief. The epidural catheter was removed postoperatively, and the analgesic pump was activated following catheter integrity confirmation.
2.3.2. Postoperative analgesia regimen
Observation group: Esketamine (0.25 mg/kg, diluted to 5 mL) was administered intravenously after the delivery and clamping of the umbilical cord. Postoperative analgesia was delivered via a patient-controlled intravenous analgesia pump, designed to avoid the risks associated with epidural analgesia (e.g., catheter displacement, infection). The analgesic mixture for the patient-controlled intravenous analgesia pump included: esketamine (1 mg/kg), butorphanol (0.15 mg/kg), and tropisetron (0.3 mg/kg), diluted to 100 mL with saline. The pump was programmed with a bolus dose of 3 mL, a PCA dose of 2 mL, and a lockout interval of 20 minutes. This approach allowed for continuous low-dose infusion of esketamine while providing adequate postoperative analgesia and maintaining a light sedation level.
Control group: The control group received the same anesthesia and analgesia regimen as the observation group, except that esketamine was replaced with normal saline (5 mL). Participants in the control group were kept fully awake during surgery, in contrast to the light sedation achieved in the observation group.
The analgesic agents used in both groups included: esketamine (Jiangsu Hengrui Medicine Co., Ltd., Nanjing, Jiangsu Province, China, National Drug Approval Number: H20193336), butorphanol (Jiangsu Hengrui Medicine Co., Ltd., National Drug Approval Number: H20020454), and tropisetron (Hangzhou Minsheng Pharmaceutical Co., Ltd., Hangzhou, Zhejiang Province, China, National Drug Approval Number: H20052664).
2.4. Outcome measures
Demographic data: Demographic information, including age, BMI, parity, gestational age, duration of surgery, and blood loss during surgery, was collected for analysis.
Adverse events: The occurrence of adverse events within 48 hours postoperatively was recorded, including dizziness, headache, nausea/vomiting, sedation (Ramsay score > 4), respiratory depression (SpO₂ < 85% or respiratory rate < 8 breaths/min), and neuroexcitatory effects (delirium, illusions, and hallucinations).
Postoperative pain scores: Pain was assessed using the Visual Analog Scale (VAS) at 4, 12, 24, and 48 hours postoperatively, considering both resting pain and uterine contraction pain. VAS scores range from 0 to 10, with higher scores indicating more severe pain.
Postoperative sedation scores: Sedation levels were evaluated using the Ramsay Sedation Scale at 4, 12, 24, and 48 hours postoperatively. The sedation levels were assessed using a scale ranging from 1 to 6: a score of 1 indicated agitation and anxiety, 2 represented a cooperative and calm state, 3 signified the ability to obey commands, 4 referred to a sleeping state but responsive to stimuli, 5 indicated difficulty in awakening, and 6 denoted unresponsiveness. A score between 2 and 4 was considered to reflect acceptable sedation, while scores of 5 and 6 were categorized as excessive sedation.
Sleep quality assessment: The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality at baseline (preoperatively), and again at 3 days, 1 week, and 4 weeks postoperatively. Higher total PSQI scores (ranging from 0–21) indicate poorer sleep quality.
Postpartum depression: Postpartum depression was evaluated using the Edinburgh Postnatal Depression Scale (EPDS) at baseline and at 3 days, 1 week, and 4 weeks postoperatively. A score > 10 suggests possible postpartum depression, and a score > 13 indicates a diagnosis of postpartum depression.
Postpartum anxiety: Anxiety was assessed using the Postpartum Anxiety Scale (PAS) at baseline, and again at 3 days, 1 week, and 4 weeks postoperatively. Higher PAS scores reflect more severe anxiety symptoms and greater need for intervention.
Postoperative recovery time: Recovery time indicators, including the first passing of gas, the first bowel movement, time to ambulation, and hospital discharge time, were recorded as measures of postoperative recovery and the effectiveness of the intervention.
2.5. Statistical analysis
Data were analyzed using SPSS 23.0 software (IBM, Armonk). Continuous variables are presented as mean ± standard deviation (SD). Comparisons between groups were performed using independent samples t tests, while intragroup comparisons were conducted using paired t tests. Categorical data were analyzed using the Chi-square test. P < .05 was considered statistically significant.
3. Results
3.1. Comparison of general data
There were no statistically significant differences between the 2 groups in terms of age, BMI, gestational age, number of previous deliveries, operation time, anesthesia time, or intraoperative blood loss (Table 1). Specifically, the age (29.56 ± 4.36 vs 30.34 ± 5.03, P = .355), BMI (26.95 ± 2.34 vs 27.73 ± 4.87, P = .252), and other baseline characteristics showed no significant differences, indicating that the 2 groups were comparable in terms of their general characteristics, thus providing a balanced foundation for the subsequent analyses.
Table 1.
Comparisons of general information between the 2 groups (N/%, X ± SD, M).
| Variable | Observation group (N = 64) | Control group (N = 61) | Z/t/χ² | P value |
|---|---|---|---|---|
| Age (yr) | 29.56 ± 4.36 | 30.34 ± 5.03 | −0.922 | .355 |
| BMI (kg/m²) | 26.95 ± 2.34 | 27.73 ± 4.87 | −1.133 | .252 |
| Gestational age (days) | 272 (266, 277) | 273 (269, 279) | 0.242 | .581 |
| Parity (n) | 0.594 | .871 | ||
| 2 | 54 (84.38%) | 54(88.53%) | ||
| 3 | 7 (10.94%) | 5 (8.20%) | ||
| 4 | 1 (1.56%) | 1 (1.64%) | ||
| Operation duration (min) | 47.25 ± 5.13 | 46.03 ± 4.37 | 1.435 | .152 |
| Anesthesia time (min) | 53.28 ± 5.26 | 52.13 ± 4.71 | 1.290 | .198 |
| Intraoperative blood loss (mL) | 222.14 ± 38.79 | 220.65 ± 35.49 | 0.225 | .823 |
BMI = body mass index, SD = standard deviation.
3.2. Comparison of postoperative adverse events
No significant differences were observed between the 2 groups regarding the incidence of postoperative adverse events. Common adverse reactions, including dizziness, headache, nausea and vomiting, and drowsiness, were relatively infrequent in both groups, with no statistically significant differences (P > .05). For instance, the incidence of postoperative nausea and vomiting was 7.81% in the observation group and 13.11% in the control group (P = .332). Although the incidence of drowsiness was slightly higher in the observation group (4.69%) compared to the control group (1.64%), this difference did not reach statistical significance (P = .333) (Table 2).
Table 2.
Comparison of postoperative adverse events between the 2 groups (N/%).
| Adverse events | Observation group (N = 64) | Control group (N = 61) | χ² | P value |
|---|---|---|---|---|
| Dizziness | 2 (3.13%) | 5 (8.20%) | 1.520 | .217 |
| Headache | 1 (1.56%) | 2 (3.28%) | 0.393 | .529 |
| Nausea and vomiting | 5 (7.81%) | 8 (13.11%) | 0.943 | .332 |
| Drowsiness | 3 (4.69%) | 1 (1.64%) | 0.936 | .333 |
| Respiratory depression | 1 (1.56%) | 3 (4.92%) | 1.136 | .287 |
| Neurological excitement symptoms | 0 (0.00%) | 0 (0.00%) | – | – |
3.3. Comparison of postoperative pain scores at different time points
At various postoperative time points, the VAS pain scores during both resting and uterine contraction states were significantly lower in the observation group, particularly at 12, 24, and 48 hours. Specifically, the resting VAS scores at 12 hours were 2.13 ± 0.38 (observation group) versus 2.53 ± 0.51 (control group), P < .001; at 24 hours, 1.78 ± 0.27 (observation group) versus 2.01 ± 0.29 (control group), P < .001; and at 48 hours, 1.41 ± 0.39 (observation group) versus 1.72 ± 0.37 (control group), P < .001. Similar differences were observed in the VAS scores during uterine contractions at all time points, indicating that esketamine provided a significant advantage in the management of postoperative pain (Table 3).
Table 3.
VAS scores at rest or during contractions at different time points postoperatively in both groups (X ± SD).
| Time point | Observation group (N = 64) | Control group (N = 61) | t | P value |
|---|---|---|---|---|
| VAS scores at rest | ||||
| 4 h | 2.63 ± 0.54 | 2.73 ± 0.62 | −0.960 | .338 |
| 12 h | 2.13 ± 0.38 | 2.53 ± 0.51 | −4.952 | <.001 |
| 24 h | 1.78 ± 0.27 | 2.01 ± 0.29 | −4.587 | <.001 |
| 48 h | 1.41 ± 0.39 | 1.72 ± 0.37 | −4.559 | <.001 |
| VAS scores during contractions | ||||
| 4 h | 3.52 ± 0.54 | 3.62 ± 0.59 | −0.987 | .327 |
| 12 h | 3.03 ± 0.61 | 3.32 ± 0.57 | −2.752 | .006 |
| 24 h | 2.27 ± 0.43 | 2.68 ± 0.43 | −5.328 | <.001 |
| 48 h | 1.53 ± 0.56 | 2.14 ± 0.56 | −6.096 | <.001 |
SD = standard deviation, VAS = Visual Analog Scale.
3.4. Comparison of postoperative sedation scores at different time points
With regard to sedation scores (Ramsay score), there was no significant difference between the 2 groups at 4 hours postoperatively (P = .936). However, at 12 and 24 hours, the observation group exhibited more pronounced sedation. For example, at 24 hours, the sedation score in the observation group was 2.28 ± 0.31, significantly higher than 2.13 ± 0.43 in the control group (P = .028). These findings suggest that esketamine may positively influence postoperative sedation in parturients (Table 4).
Table 4.
Ramsay sedation scores at different time points postoperatively in both groups (X ± SD).
| Time point | Observation group (N = 64) | Control group (N = 61) | t | P value |
|---|---|---|---|---|
| 4 h | 2.57 ± 0.73 | 2.56 ± 0.68 | 0.079 | .936 |
| 12 h | 2.46 ± 0.52 | 2.30 ± 0.48 | 1.788 | .075 |
| 24 h | 2.28 ± 0.31 | 2.13 ± 0.43 | 2.224 | .028 |
| 48 h | 2.02 ± 0.19 | 2.04 ± 0.26 | −0.489 | .650 |
SD = standard deviation.
3.5. Comparison of postoperative sleep quality at different time points
Postoperative sleep quality, assessed by the PSQI, was significantly better in the observation group at 3 days, 1 week, and 4 weeks compared to the control group. At 3 days postoperatively, the PSQI score in the observation group was 11.25 ± 1.07, significantly lower than 12.41 ± 2.43 in the control group (P = .002). At 1 week, the PSQI score in the observation group was 10.13 ± 1.73, notably lower than 11.53 ± 1.37 in the control group (P < .001) (Table 5).
Table 5.
PSQI scores at different time points postoperatively in both groups (X ± SD).
| Time point | Observation group (N = 64) | Control group (N = 61) | t | P value |
|---|---|---|---|---|
| −1 d | 10.95 ± 1.78 | 10.44 ± 1.92 | 1.539 | .132 |
| 3 d | 11.25 ± 1.07 | 12.41 ± 2.43 | −3.417 | .002 |
| 1 wk | 10.13 ± 1.73 | 11.53 ± 1.37 | −5.027 | <.001 |
| 4 wk | 9.26 ± 2.03 | 10.17 ± 1.55 | −2.833 | .008 |
PSQI = Pittsburgh Sleep Quality Index, SD = standard deviation.
3.6. Comparison of postoperative depression and anxiety levels at different time points
In the evaluation of postoperative depression and anxiety, the observation group demonstrated significant improvements in both depression (EPDS score) and anxiety (PAS score) levels compared to the control group. At 3 days, 1 week, and 4 weeks postoperatively, the EPDS and PAS scores in the observation group were significantly lower than those in the control group, with statistical significance. For example, at 3 days postoperatively, the EPDS score in the observation group was 8.95 ± 1.47, significantly lower than 11.37 ± 2.71 in the control group (P < .001). In terms of anxiety, at 4 weeks, the PAS score in the observation group was 8.94 ± 3.86, significantly lower than 10.72 ± 4.21 in the control group (P = .015) (Table 6).
Table 6.
Levels of depression (EPDS scores) and anxiety (PAS scores) assessment at different time points postoperatively in both groups (X ± SD).
| Time point | Observation group (N = 64) | Control group (N = 61) | t | P value |
|---|---|---|---|---|
| Depression (EPDS scores) | ||||
| −1 d | 6.15 ± 1.38 | 5.91 ± 1.62 | 0.891 | .375 |
| 3 d | 8.95 ± 1.47 | 11.37 ± 2.71 | −6.160 | <.001 |
| 1 wk | 10.25 ± 2.31 | 13.31 ± 2.18 | −7.620 | <.001 |
| 4 wk | 7.46 ± 1.58 | 9.25 ± 1.53 | −6.430 | <.001 |
| Anxiety (PAS scores) | ||||
| −1 d | 18.78 ± 5.21 | 19.89 ± 5.08 | −1.208 | .227 |
| 3 d | 15.53 ± 4.85 | 17.83 ± 5.32 | −2.524 | .012 |
| 1 wk | 11.18 ± 4.12 | 13.48 ± 4.67 | −2.918 | .004 |
| 4 wk | 8.94 ± 3.86 | 10.72 ± 4.21 | −2.461 | .015 |
EPDS = Edinburgh Postnatal Depression Scale, PAS = Postpartum Anxiety Scale, SD = standard deviation.
3.7. Comparison of postoperative recovery between the 2 groups
Regarding postoperative recovery, no significant differences were observed between the 2 groups in terms of hospitalization duration, time to first bowel movement, time to first passage of gas, or time to first ambulation. For example, the hospitalization time was 102.56 hours in the observation group, slightly longer than the 99.15 hours in the control group, but no significant difference was noted (P = .835). Additionally, no significant differences were found in other recovery indicators, suggesting that esketamine had a minimal impact on the overall postoperative recovery (Table 7).
Table 7.
Comparison of postoperative recovery between the 2 groups (M).
| Time (h) | Observation group (N = 64) | Control group (N = 61) | Z | P value |
|---|---|---|---|---|
| Postpartum hospital stay | 102.56 (95.82, 117.37) | 99.15 (96.27, 114.64) | 0.124 | .835 |
| Time to first bowel movement | 65.78 (53.37, 84.87) | 73.06 (55.47, 86.38) | 0.813 | .437 |
| Time to first flatus | 12.53 (10.38, 16.71) | 13.45 (11.19, 15.86) | 1.072 | .286 |
| Time to first ambulation | 25.29 (22.16, 26.39) | 25.32 (22.42, 27.82) | 0.523 | .617 |
4. Discussion
This study utilized a retrospective cohort design to evaluate the efficacy of esketamine in postoperative analgesia following cesarean delivery, while also exploring its effects on maternal postoperative anxiety, depression, and sleep quality. The findings suggest that esketamine offers significant benefits in terms of pain relief, sedation, sleep quality improvement, and the alleviation of postoperative anxiety and depression, without a noticeable increase in adverse events. These results provide strong support for its clinical application.
Firstly, esketamine demonstrated superior efficacy in managing postoperative pain compared to conventional treatments. The VAS scores for both resting and uterine contraction pain at 12, 24, and 48 hours post-surgery were significantly lower in the observation group, indicating that esketamine effectively alleviates postoperative pain. Previous studies have shown that esketamine exerts potent analgesic effects through NMDA receptor antagonism, with minimal side effects.[24] Our findings align with this literature, further confirming the drug’s efficacy in postoperative pain management.
Secondly, esketamine had a marked effect on postoperative sedation. The Ramsay Sedation Scale scores at 12 and 24 hours postoperatively were significantly higher in the observation group, indicating that esketamine effectively alleviates postoperative anxiety and enhances overall comfort. Moderate sedation can alleviate discomfort in parturients, thus facilitating recovery.[25]
In terms of sleep quality, esketamine demonstrated clear benefits. The PSQI scores at 3 days, 1 week, and 4 weeks postoperatively were significantly lower in the observation group, suggesting a substantial improvement in sleep quality. Postoperative sleep disturbances are common among parturients, and esketamine, through its analgesic and sedative effects, indirectly improved sleep quality, supporting both physical and psychological recovery.[26]
Regarding anxiety and depression, the study revealed that the observation group had significantly lower scores on the EPDS and the PAS at 3 days, 1 week, and 4 weeks post-surgery. These results indicate that esketamine is effective in alleviating both postoperative anxiety and depression. Esketamine may improve maternal mental health through multiple mechanisms, such as modulation of neurotransmitter systems, reduction of pain, and enhancement of sleep, thereby promoting psychological well-being.[27,28]
Regarding safety, despite the use of esketamine in the observation group, no significant differences were observed in the incidence of postoperative adverse events between the 2 groups, and no severe adverse reactions, such as respiratory depression or neuroexcitation, occurred. This indicates that esketamine, within the dosage range used in this study, demonstrates a favorable safety profile and can be considered safe for clinical use.[29]
Despite these promising findings, this study has several limitations. Firstly, the retrospective cohort design may introduce selection bias. Although we matched groups based on key baseline characteristics (e.g., age, BMI, ASA classification), the non-randomized allocation of analgesic methods could still lead to unaccounted-for differences. This may affect the internal validity of the results. To minimize this bias, future studies with randomized controlled designs or propensity score matching are recommended. Secondly, the study was conducted at a single center, which limits the generalizability of the findings. The patient population and clinical protocols may vary in other settings, making it difficult to apply these results universally. The small sample size further limits the ability to detect subtle differences between groups and may reduce statistical power. To address these issues, multicenter studies with larger sample sizes are needed to improve external validity and provide more robust evidence for the widespread application of esketamine. Thirdly, the absence of long-term follow-up prevented the evaluation of esketamine’s sustained effects on maternal mental health, particularly the persistence of improvements in anxiety, depression, and sleep quality over time. Future research should include longer follow-up periods to assess whether the observed benefits are sustained or if any long-term side effects emerge. Lastly, this study did not directly compare esketamine with other commonly used analgesic agents, such as opioids or local anesthetics. A head-to-head comparison would provide a clearer understanding of esketamine’s relative efficacy, safety, and advantages over other treatment options. Future research should include multicenter, large-sample, randomized controlled trials to further validate the findings, minimize selection bias, and overcome the limitations of sample size and single-center design.
In conclusion, esketamine possesses potential for effective postoperative pain management following cesarean delivery, with promising effects on improving maternal sleep quality and alleviating anxiety and depression. Furthermore, it appears to have a good safety profile. However, further studies are needed to explore its long-term effects and compare its performance with other analgesic options to provide more robust evidence for its inclusion in comprehensive maternal care.
Author contributions
Conceptualization: Bing Zhang, Qun Zhou.
Data curation: Bing Zhang, Qun Zhou.
Formal analysis: Bing Zhang, Qun Zhou.
Methodology: Qun Zhou.
Validation: Qun Zhou.
Visualization: Bing Zhang, Qun Zhou.
Writing – original draft: Bing Zhang, Qun Zhou.
Writing – review & editing: Bing Zhang, Qun Zhou.
Abbreviations:
- BMI
- body mass index
- EPDS
- Edinburgh Postnatal Depression Scale
- PAS
- Postpartum Anxiety Scale
- PSQI
- Pittsburgh Sleep Quality Index
- VAS
- Visual Analog Scale
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Zhang B, Zhou Q. Esketamine for postoperative analgesia after cesarean section: Effects on pain, mood, sleep quality, and safety. Medicine 2025;104:37(e44432).
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