This retrospective study evaluated the efficacy of epidural esketamine and the conventional adjuvant sufentanil for labor analgesia, as well as the impact on postpartum depression, maternal and neonatal outcomes, and associated adverse effects. Our study found that epidural 0.3 mg/ml esketamine for labor analgesia might be associated with more effective sedation, shorter duration of second-stage labor, lower PPD incidence, lower pruritus rate, and no significant effect on the motor block and maternal and infant outcomes compared with epidural 0.3 µg/ml sufentanil. Nevertheless, its analgesic efficacy was marginally inferior to that of sufentanil; however, this minor discrepancy was not clinically important.

Esketamine is a rotary isomer of ketamine that has an affinity for NMDA receptors whose analgesic effect is approximately 1.5 to 2 times that of ketamine [7,8,9]. The analgesic, sedative, and anesthetic actions of esketamine are thought to be derived from its blocking action on NMDA receptors [7, 9, 14]. Esketamine antagonizes the NMDA receptor and inhibits its activation by glutamate. It also binds to central opioid μ- and δ-receptors, activating the downstream anti-injury sensory system and exerting analgesic effects [7, 9, 14, 22].

Epidural esketamine combined with 0.075% ropivacaine induced dose-dependent dizziness, which was notably common when the esketamine dose was 1 mg/ml, according to a dose exploration study [23]. Under the results of the pre-test, the present investigation employed a small dose of 0.3 mg/ml of esketamine in conjunction with 0.083% ropivacaine based on the results of pre-test. In this trial, the sufentanil group received the usual epidural anesthetic medication combination of 0.083% ropivacaine and 0.3 µg/ml sufentanil, which is the traditional protocol in our hospital.

In comparison to the sufentanil group, the esketamine group’s VAS scores were marginally higher at t1-4, which means the analgesic effect was marginally less effective. However, the difference in the actual maternal perception of pain between the two groups was not apparent after analgesia, indicating that the VAS scores of the two groups, despite being statistically distinct, may not have clinical significance.

This could be due to the favorable sedative effect, but it also suggests that the amount of esketamine employed in this experiment might not be the ideal dose for epidural labor analgesia, and future prospective studies are needed. Research has demonstrated that esketamine might be more appropriate to combine with opioids rather than be employed as a single epidural adjuvant [24]. The Ramsay sedation scores of Group ER in this trial were higher at t1-3 after analgesia, which may suggest there is a faster onset of sedation when epidural esketamine is administered for labor analgesia.

Research has demonstrated that the novel antidepressant drug esketamine achieves its rapid and potent antidepressant effects by combining a variety of mechanisms, such as antagonizing NMDA receptors, increasing brain-derived neurotrophic factor (BDNF) release, inhibiting neuronal apoptosis, and inducing synaptic plasticity [25]. Studies have proven that perioperative esketamine administered intravenously or utilized for postoperative intravenous self-controlled analgesia (PCIA) reduces the incidence of postoperative EPDS scores and PPD in women after cesarean section or delivery and improves the analgesic effect [6, 26, 27]. Our study observed that the EPDS score and PPD prevalence on the 42nd day postpartum were significantly reduced in women receiving epidural esketamine, which may suggest that esketamine used for epidural labor analgesia seems to be related to a lower incidence of postpartum depression in women with vaginal delivery. It has been proposed that the sensory-motor blocking effect caused by epidural local anesthetics has some effect on uterine contraction [28]. The KR group exhibited a significantly shorter second stage of labor than the SR group in this experiment. It was postulated that this may be attributed to the KR group’s reduced dosage of local anesthetic ropivacaine, which decreased the effect on uterine contraction, shortened the second stage of labor, and improved the delivery outcome. Esketamine inhibits opioid-induced nociceptive hypersensitivity by antagonizing the NMDA receptor, allowing for lower opioid dosages with less impact on mother and infant and fewer neurological adverse effects [7, 9, 14]. Group KR showed a decreased rate compared to Group SR in our study without other adverse reactions.

This study’s limitations include the following: Firstly, the absence of a blank control group using a purely local anesthetic agent. Due to the poor analgesic effects, cases of labor analgesia with epidural ropivacaine alone were few, and beyond our certain period, which hindered us from drawing some of the conclusions. Further research including cases of labor analgesia with epidural ropivacaine alone is still necessary. Secondly, it is difficult to determine the equivalent dose of esketamine and sufentanil for epidural analgesia, which may affect the results of the study. Thirdly, the retrospective nature of the study prevented the collection of the amount of epidural labor analgesia medication consumed. Last is the failure to establish different dosages of esketamine to analyze the optimal dosage of esketamine PCEA for labor analgesia. Prospective clinical trials with larger samples will be conducted in the future to investigate the optimal ratios and doses of esketamine.