Analgesic Effect of Esketamine Combined with Tramadol for Patient-Controlled Intravenous Analgesia After Cesarean Section: A Randomized Controlled Trial

Purpose: High rate of cesarean section (CS) bring challenges to analgesic management after CS. Previous studies state that adjuvant treatment with a low dose of esketamine intraoperatively could reduce postoperative pain and opioid consumption, and even prevent postpartum depression. However, few researches involve in patient-controlled intravenous analgesia (PCIA) with esketamine after CS. In this trial, we explored a new combination of esketamine with tramadol for PCIA after CS with the aim to provide a better analgesic regimen for use in the clinic. Patients and Methods: 170 puerperae undergoing CS were recruited for this trial and randomly assigned into 2 groups (1:1): The control group received a formula of PCIA with butorphanol 0.1mg/kg and tramadol 400mg postoperatively, while the intervention group received a formula of PCIA with esketamine 1mg/kg and tramadol 400mg. The primary outcome was the mean numerical rating scale (NRS) scores at rest, sitting, and uterine contraction at 6 hours postoperatively. The second outcomes included the mean NRS scores at rest, sitting, and uterine contraction at 12, 24, and 48 hours postoperatively. The incidence of adverse events, postoperative sedation, postoperative sleep quality, maternal satisfaction regarding postoperative analgesia and the Edinburgh postnatal depression scale (EPDS) score were also be evaluated. Results: The mean (SD) of the mean NRS scores at rest, sitting, and during uterine contraction at 6 hours postoperatively were 4.8 (0.7) points in the intervention group and 5.3 (0.5) points in the control group. The estimated mean difference between the two groups at 6 hours postoperatively was -0.5 points (95% confidence interval [CI], -0.7 to -0.3; P < 0.001). Compared with the control group, the patients in the intervention group had a significantly lower mean pain intensity at 12 and 24 hours postoperatively (-0.5 points [95% CI, -0.6 to -0.3]; P < 0.001 and -0.2 points [95% CI, -0.4 to 0]; P = 0.019 respectively). Otherwise, differences at 48 hours after surgery between the two groups were nonsignificant (0 points [95% CI, -0.2 to 0.2]; P = 0.802). The incidence of adverse events in the intervention group (11.8%) was significantly lower than in the control group (24.7%) (ratio difference -12.9, [95% CI, -24.3 to -1.5]; P = 0.029). No difference was found in postoperative sleep quality (P = 0.765), analgesic satisfaction (P= 0.818) and EPDS scores (P = 0.154) between the two groups. Conclusion: