Determination of the ED90 for Epidural Hydromorphone and Morphine for Postoperative Pain Using a Biased-Coin Up-and-Down Sequential Design After Elective Cesarean Delivery

Background: Hydromorphone and morphine are the primary opioids recommended for epidural analgesia following cesarean delivery. This study aimed to determine the 90% effective dose (ED90) of epidural hydromorphone and morphine in this patient population. Methods: In this dose-finding trial, 80 patients undergoing cesarean delivery under combined spinal-epidural anesthesia (CSEA) were randomized to receive a single epidural injection of either hydromorphone or morphine after uterine closure. The dose of each agent was determined using a biased-coin up-and-down sequential allocation method to estimate the ED90. In addition, all patients received standardized multimodal analgesia postoperatively. Satisfactory analgesia was defined as a visual analogue scale (VAS) score ≤ 3 within 12 hours after cesarean delivery, without the need for supplemental opioids. Results: The estimated ED90 was 500 μg (95% confidence interval [CI], 495.00– 532.50 μg) for epidural hydromorphone and 3 mg (95% CI, 2.97– 3.21 mg) for epidural morphine. Comparative analyses of postoperative VAS scores, adverse effects (nausea/vomiting and pruritus), and rescue hydromorphone consumption revealed no statistically significant differences between the two dosage groups. Conclusion: The ED90 for post-cesarean analgesia was estimated to be 500 μg for epidural hydromorphone and 3 mg for epidural morphine. There were no statistically significant differences in adverse effects between the two drugs at their respective ED90 doses. Clinical Trial Registration: ChiCTR2400084510.