Obstetrics & Gynecology · Medical Literature
Effect of Oliceridine on the Acute Postoperative Pain Management After Elective Cesarean Delivery: A Randomized Non-Inferiority Trial.
Abstract
Effective postoperative analgesia following cesarean delivery is crucial for maternal recovery. Sufentanil, commonly administered via patient-controlled intravenous analgesia (PCIA), is associated with dose-dependent adverse effects, particularly gastrointestinal disturbances. Oliceridine, a novel G protein-biased μ-opioid receptor agonist, offers the dual advantage of potent analgesia and a reduced risk of opioid-related adverse events. This study aimed to compare the analgesic efficacy and the incidence of side effects between the G protein-biased μ-opioid receptor agonist oliceridine and the conventional opioid sufentanil. In this single-center, randomized, double-blind, non-inferiority trial, women undergoing elective cesarean delivery under combined spinal-epidural anesthesia (CSEA) were randomly assigned to receive either oliceridine or sufentanil via patient-controlled intravenous analgesia (PCIA) for 48 hours postoperatively. The primary outcome was the sum of pain intensity differences over 48 hours (SPID48), calculated from resting Numerical Rating Scale (NRS) scores (0-10) assessed at 0, 12, 24, 36, and 48 hours postoperatively. Secondary outcomes included the sum of pain intensity differences at 12 h, 24 h, and 36 h, total PCIA demand, rescue analgesia utilization, time to first lactation, maternal satisfaction, and incidence of adverse events. 160 participants were included in the final analysis. The primary outcome, SPID48, showed an adjusted mean of 172.50 (95% CI, 163.37-181.63) in the oliceridine group and 147.90 (95% CI, 137.59-158.21) in the sufentanil group (mean difference 24.60; 95% CI, 10.83-38.37). The lower limit of the 95% CI for the difference exceeded the pre-specified non-inferiority margin of -20, establishing non-inferiority of oliceridine. Oliceridine provides non-inferior postoperative analgesic efficacy compared with sufentanil in women undergoing cesarean delivery. Exploratory observations suggested a lower incidence of nausea and higher patient satisfaction in the oliceridine group; these findings are hypothesis-generating and require further validation.
Clinical relevance
Effective multimodal analgesia after cesarean delivery is a critical determinant of maternal recovery, early ambulation, and breastfeeding initiation, yet conventional PCIA opioids such as sufentanil carry a well-established burden of gastrointestinal adverse effects that can compromise these outcomes. Oliceridine, a G protein-biased µ-opioid receptor agonist, selectively activates the analgesic G protein pathway while minimizing β-arrestin-2 recruitment — the pathway implicated in opioid-related side effects such as nausea, vomiting, and respiratory depression — offering a mechanistically distinct alternative. As cesarean delivery is one of the most commonly performed surgical procedures worldwide, demonstrating a non-inferior and potentially better-tolerated analgesic option has immediate and broad clinical relevance for obstetric anesthesiology practice.
Key findings
1. PRIMARY OUTCOME — NON-INFERIORITY ESTABLISHED: The Sum of Pain Intensity Differences over 48 hours (SPID48) was 172.50 (95% CI, 163.37–181.63) in the oliceridine group versus 147.90 (95% CI, 137.59–158.21) in the sufentanil group; mean difference +24.60 (95% CI, 10.83–38.37). The lower bound of the 95% CI (+10.83) exceeded the pre-specified non-inferiority margin of −20, formally establishing non-inferiority of oliceridine. 2. DIRECTION OF EFFECT — POTENTIAL SUPERIORITY SIGNAL: The point estimate and entire 95% CI for the mean difference in SPID48 favored oliceridine over sufentanil, suggesting oliceridine may provide numerically superior resting pain control across the 48-hour postoperative window, though the trial was powered for non-inferiority rather than superiority. 3. ADVERSE EFFECT PROFILE — NAUSEA: Exploratory analysis indicated a lower incidence of nausea in the oliceridine group compared with sufentanil; exact event rates and inferential statistics (OR, RR, or p-values) were not reported in the abstract and should be sought in the full publication. 4. PATIENT SATISFACTION: Maternal satisfaction scores were reported to be higher in the oliceridine group on exploratory analysis; quantitative satisfaction data and statistical parameters are not provided in the abstract and are hypothesis-generating pending full-text review. 5. STUDY DESIGN AND POPULATION: This was a single-center, randomized, double-blind, non-inferiority RCT enrolling 160 women undergoing elective cesarean delivery under combined spinal-epidural anesthesia (CSEA), with PCIA administered for 48 hours postoperatively; NRS pain scores were captured at 0, 12, 24, 36, and 48 hours. 6. SECONDARY OUTCOMES ASSESSED: Pre-specified secondary endpoints included SPID at 12 h, 24 h, and 36 h; total PCIA demand; rescue analgesia utilization; and time to first lactation — specific quantitative results for these endpoints are not reported in the abstract and limit definitive conclusions beyond the primary outcome.
Practice implications
For women undergoing elective cesarean delivery under neuraxial anesthesia who require PCIA-based postoperative opioid analgesia, oliceridine represents a non-inferior alternative to sufentanil and may be preferentially considered in patients at elevated risk for opioid-induced nausea and vomiting (OINV) or in whom early breastfeeding initiation is a priority, given the exploratory signals of reduced nausea and higher satisfaction. Clinicians should note that this evidence derives from a single-center non-inferiority trial with exploratory secondary endpoints; optimal oliceridine PCIA dosing, lockout intervals, and maximum dose parameters specific to the postpartum population should be confirmed from the full publication before protocol implementation. Further adequately powered, multicenter RCTs are needed to validate the nausea reduction and satisfaction benefits as superiority claims, to characterize the lactation and neonatal safety profile in breastfeeding dyads, and to define the role of oliceridine within enhanced recovery after cesarean (ERAC) pathways.