Exploring the Analgesic Efficacy and mechanisms of low-dose esketamine in pregnant women undergoing cesarean section: A randomized controlled trial

Background: Postoperative pain is a prevalent concern following a cesarean section. This study aimed to investigate the effect and mechanism of low-dose (0.1 mg/kg) esketamine on postoperative pain management in pregnant women undergoing cesarean sections, specifically in cases where both patient-controlled intravenous analgesia (PCIA) and patient-controlled epidural analgesia (PCEA) were employed. Methods: Pregnant women intending to undergo elective cesarean section were divided into four subgroups based on the intravenous administration of esketamine and the specific analgesia methods employed: E1 (0.1 mg/kg esketamine + PCEA), E2 (0.1 mg/kg esketamine + PCIA), C1 (saline + PCEA), and C2 (saline + PCIA). The primary outcome was the maximum pain score within 24 h postoperatively. Secondary outcomes included the pressure pain threshold and tolerance at 30 min and 24 h postoperatively, along with the inflammation and adverse event index scores. Results: A total of 118 pregnant women were assigned to the four groups: E1 (n = 29), E2 (n = 29), C1 (n = 30), and C2 (n = 30). Compared with those in the control groups (C1 + C2), the maximum postoperative pain scores within 24 h in the esketamine groups (E1 + E2) were significantly lower (4 [2-5] vs. 4 [4-6], P = 0.002), and the E1 group exhibited superior analgesic effects compared with other groups. No significant differences were observed in postoperative hyperalgesia or inflammation across the four groups. Notably, esketamine combined with PCIA increased the incidence of postoperative nausea and vomiting (7 [25 %] vs. 0 [0 %]; P = 0.005). Conclusion: The administration of low-dose (0.1 mg/kg) esketamine effectively alleviates pain following cesarean section, and the analgesic effect is notably enhanced in combination with PCEA. Importantly, these effects do not appear to be mediated through anti-inflammatory mechanisms or the inhibition of hyperalgesia. Clinical trial registration number: NCT05414006.