Background: Prior research has established that esketamine, the S-isomer of ketamine, demonstrates greater NMDA receptor binding affinity and superior analgesic effects. Nevertheless, the optimal dosage of esketamine combined with ropivacaine for early epidural analgesia in nulliparous women during the first stage of labor remains undetermined. This prospective, double-blind, sequential dose-finding study aimed to estimate the 90% effective dose (ED 90 ) of epidural esketamine for this population to minimize dose-related adverse effects. Methods: The study included forty nulliparous women with cervical dilation between 2– 4 cm who requested epidural analgesia. Participants initially received 10 mL of 0.08% ropivacaine (8 mg ropivacaine) along with research dose of epidural esketamine, starting at 5 mg. Subsequent doses were adjusted using the biased coin up-down (BCUD) sequential allocation method based on prior participant responses. Analgesic success was defined as maintaining a Numeric Rating Scale (NRS) pain score of ≤ 3 at 15-, 30-, and 45-minutes post-administration. The ED 90 and its 95% confidence interval (CI) were derived via isotonic regression analysis. The primary endpoint was the ED 90 of esketamine combined with 0.08% ropivacaine for early epidural labor analgesia. Secondary outcomes and adverse events were also documented. Results: Our study found that the ED 90 of epidural esketamine for early first-stage labor analgesia in nulliparous women was 8.05 mg (95% CI: 5.96– 8.58 mg). The median upper sensory level of analgesia was T9 (interquartile range: T8 to T10). The median modified Bromage score was 0, and the median Ramsay sedation score was 2. Conclusion: The ED 90 of epidural esketamine combined with 0.08% ropivacaine for early labor analgesia in nulliparous women is approximately 8 mg, optimizing pain relief while minimizing dose-related side effects. Trial Registration: ChiCTR2400085308, http://www.chictr.org.cn . Registration Time: 2024.06.05. Keywords: ED 90 , esketamine, epidural labor analgesia, nulliparous women, early first stage of labor
Lin et al. (2026) studied this question.