Esketamine as an opioid-sparing adjuvant for epidural labour analgesia: a randomised, double-blind trial evaluating...

Opioid-based epidural analgesia, while effective, is frequently associated with maternal side effects such as pruritus and potential central sensitisation. Esketamine provides rapid analgesic and antidepressant effects at subanesthetic doses. We compared esketamine with sufentanil both added to 0.083% ropivacaine focusing on efficacy, maternal safety, and postpartum depression outcomes.

In this single-centre, randomised, double-blind, controlled trial, 200 nulliparous parturients (ASA I-II, 18-40 years, cervical dilatation 2-3 cm) requesting epidural analgesia were equally allocated to receive patient-controlled epidural analgesia (PCEA) containing either sufentanil 0.3 µg/ml or esketamine 0.3 mg/ ml combined with ropivacaine 0.083%. Primary outcomes included analgesic onset time, maximum sensory block level and Edinburgh Postnatal Depression Scale (EPDS) at 42 days postpartum. Secondary outcomes included adverse events, VAS scores and neonatal Apgar scores.

Between December 2024 and May 2025, 197 participants completed the study (98 of sufentanil, 99 of esketamine). Baseline characteristics were comparable. Esketamine significantly reduced onset time (5.9 ± 0.6 min vs. 9.8 ± 1.7 min, P < 0.001), achieved a predominant T8 sensory block (67.7% vs. 45.9%, P < 0.001) and lowered EPDS scores (5.6 ± 1.3 vs. 9.8 ± 1.5, P < 0.001). Total ropivacaine consumption throughout the first stage of labour was 17% lower in the esketamine group (12.4 ml [10.3-14.5] vs. 14.9 ml [12.6-17.2]; P < 0.001). EPDS scores at 42 days were lower with esketamine (5.6 ± 1.3 vs. 9.8 ± 1.5, P < 0.001). The incidence of probable postpartum depression (EPDS ≥13) was also reduced in the esketamine group (4.0% vs. 18.4%, P = 0.003). Maternal adverse events such as pruritus (3.0% vs. 45.9%), hypotension (4.0% vs. 38.8%), and urinary retention (3.0% vs. 22.4%) were markedly reduced with esketamine (all P < 0.001). VAS and Apgar scores were similar between groups.

Esketamine-ropivacaine epidural analgesia provides faster onset, fewer maternal side effects, and potential antidepressant benefits compared with sufentanil-ropivacaine. These findings support esketamine as a promising opioid-sparing strategy in obstetric anaesthesia.

Chinese Clinical Trial Registry, ChiCTR2500109086. Retrospectively registered on September 11, 2025.