Orthopedics · Medical Literature
Comparison of Oliceridine and Hydromorphone for Postoperative Analgesia in Adults Undergoing Lower Limb Fracture Surgery: A Randomized Controlled Non-Inferiority Trial.
Abstract
This study aimed to compare the efficacy and safety of oliceridine versus hydromorphone for patient-controlled intravenous analgesia (PCIA) following lower limb fracture surgery. A total of 126 adult patients scheduled for lower limb fracture surgery were enrolled and randomly assigned (1:1) to receive PCIA with either oliceridine or hydromorphone, both combined with flurbiprofen axetil. The study was double-blinded. The primary outcome was the non-inferiority of the resting Numeric Rating Scale (NRS) pain score at 48 hours postoperatively, with a pre-specified non-inferiority margin of 1.0. Secondary outcomes included resting NRS scores at 1, 12, 24 hours postoperatively, incidences of postoperative nausea and vomiting (PONV) and pruritus, and total analgesic consumption. Analysis of the primary endpoint revealed that the median 48-hour NRS score in the oliceridine group was non-inferior to that in the hydromorphone group within the per-protocol population (n=118). Using the Hodges-Lehmann estimator, the median difference was -0.0001 (95% CI: -0.0000, 0.0001). Since the upper confidence limit (0.0001) was less than the non-inferiority margin of 1.0, non-inferiority was established. Sensitivity analysis using a bootstrap method supported this conclusion, yielding a mean difference of 0.072 (95% CI: -0.183, 0.326). Secondary analyses indicated a significantly reduced rate of PONV in the oliceridine group within the intention-to-treat cohort (4.8% vs 15.9%, p=0.040), although this difference was marginal in the per-protocol cohort (p=0.092). No clinically relevant differences were noted in pruritus or rescue analgesia requirements. For post-operative analgesia after lower limb fracture surgery, oliceridine provides analgesic efficacy comparable to hydromorphone. Observations suggest a potential for a lower incidence of PONV with oliceridine, which may offer a favorable opioid option within multimodal analgesic regimens for this population.
Clinical relevance
In adults undergoing lower limb fracture surgery, is oliceridine non-inferior to hydromorphone when used as the opioid component of patient-controlled intravenous analgesia (PCIA) combined with flurbiprofen axetil, as measured by resting NRS pain scores at 48 hours postoperatively? __SNAPSHOT__ {"studyDesign":"Randomized controlled non-inferiority trial, double-blinded, parallel-group (1:1)","setting":"Single center; Chongqing University Central Hospital (Chongqing Emergency Medical Center), Chongqing, China. Conducted October 2025 – March 2026.","sampleSize":"n=126 enrolled (randomized 1:1); per-protocol (PP) population n=118; ITT population size not explicitly stated but implied to be 126","population":"Adult patients scheduled for elective lower limb fracture surgery requiring postoperative IV opioid-based PCIA. Specific ASA class, comorbidity profile, fracture types, and age range not reported in the abstract.","intervention":"Oliceridine via PCIA combined with flurbiprofen axetil (Group O). Specific oliceridine dosing parameters not reported in the abstract.","comparator":"Hydromorphone via PCIA combined with flurbiprofen axetil (Group H). Specific hydromorphone dosing parameters not reported in the abstract.","primaryOutcome":"Non-inferiority of resting NRS pain score at 48 hours postoperatively, with a pre-specified non-inferiority margin of 1.0 NRS point, assessed in the per-protocol population using the Hodges-Lehmann estimator.","followUp":"48 hours postoperatively (primary); secondary NRS assessments at 1, 12, and 24 hours. Overall study follow-up duration beyond 48 hours not reported in the abstract.","fundingSource":"Not reported in the abstract"}
Key findings
PRIMARY OUTCOME: Non-inferiority was established. In the per-protocol population (n=118), the median difference in 48-hour resting NRS score between the oliceridine and hydromorphone groups was −0.0001 (95% CI: −0.0000 to 0.0001) by Hodges-Lehmann estimation. The upper confidence limit (0.0001) fell well below the pre-specified non-inferiority margin of 1.0, confirming non-inferiority. Sensitivity analysis using a bootstrap method supported this conclusion, yielding a mean difference of 0.072 (95% CI: −0.183 to 0.326). SECONDARY OUTCOMES — PAIN SCORES OVER TIME: Generalized estimating equations analysis showed no significant difference in the trend of postoperative NRS scores over time between the two groups (interaction P=0.851). PONV: In the ITT cohort, PONV was significantly lower in the oliceridine group (4.8% vs. 15.9%; p=0.040). In the PP cohort, the difference was numerically similar but did not reach statistical significance (3.3% [2/60] vs. 12.1% [7/58]; p=0.092). PRURITUS: Incidence was low and comparable between groups (3.3% vs. 1.7%; p=1.000). No clinically relevant differences were noted in rescue analgesia requirements. ANALGESIC CONSUMPTION: Total prescribed volume was similar (median 95 mL [IQR 93–96] in both groups; p=0.724); however, actual opioid consumption expressed as morphine-equivalent doses was significantly lower in the oliceridine group (91.9 ± 14.1 mg vs. 100.2 ± 16.1 mg; p=0.003). The absolute difference of approximately 8.3 mg morphine equivalents (calculated) and its clinical relevance require contextual interpretation. NNT and NNH for PONV were not reported; using ITT PONV rates, NNH (for PONV with hydromorphone vs. oliceridine) = 1/(0.159 − 0.048) = approximately 9 (calculated). No serious or unexpected adverse events were reported in the abstract.
Practice implications
This double-blind RCT established that oliceridine PCIA was non-inferior to hydromorphone PCIA for resting pain control at 48 hours after lower limb fracture surgery, with a statistically robust margin of separation from the pre-specified non-inferiority threshold. The PONV signal in the ITT analysis (p=0.040) is hypothesis-generating but was not significant in the PP analysis (p=0.092), which limits firm conclusions about a safety advantage over hydromorphone specifically; notably, most prior oliceridine data compare it to morphine, not hydromorphone. The statistically significant reduction in morphine-equivalent consumption (~8.3 mg, p=0.003) is of uncertain clinical magnitude and must be weighed carefully. The findings apply to adult patients undergoing lower limb fracture surgery in a single Chinese emergency-center context. Patients with significant comorbidities (e.g., severe renal impairment, obesity, sleep apnea, pediatric or geriatric extremes), those requiring analgesia beyond 48 hours, or those in non-fracture orthopedic contexts were not adequately represented or studied. Because only the abstract is available for this review, specific dosing regimens, baseline NRS values, absolute NRS scores at each timepoint, and full adverse-event profiles cannot be assessed, which limits the completeness of this interpretation. The study does not yet provide a sufficient basis to recommend routine substitution of hydromorphone with oliceridine in this surgical context; rather, it supports feasibility and safety of oliceridine as an alternative for clinicians considering it, pending replication in larger, multicenter trials. __LIMITATIONS__ Single-center design at one Chinese emergency medical center limits generalizability across health systems, surgical volumes, and patient demographics.,Relatively small per-protocol sample (n=118); the study may be underpowered to detect meaningful differences in low-frequency adverse events such as respiratory depression, which was not reported in the abstract.,Follow-up limited to 48 hours; longer-term analgesic requirements, opioid-related adverse events (e.g., constipation, delayed respiratory depression), and patient-reported outcomes were not assessed.,The PONV finding was statistically significant in the ITT cohort but not in the PP cohort, introducing uncertainty about the robustness and directionality of this secondary finding.,Non-inferiority margin of 1.0 NRS point is clinically reasonable but was not validated against minimum clinically important difference (MCID) data specific to post-fracture surgery patients; the MCID on the NRS is typically accepted as 1–2 points, making the margin selection pivotal.,Specific oliceridine and hydromorphone dosing parameters (demand doses, loading doses, lockout intervals) are not reported in the abstract, preventing pharmacologically grounded interpretation or replication.,Only resting NRS scores were assessed; movement-evoked pain scores, which are often more clinically relevant in orthopedic fracture surgery, were not reported as a primary or secondary endpoint.,Funding source is not disclosed, preventing assessment of potential industry-related bias.,Oliceridine's comparator in most prior pivotal data is morphine, not hydromorphone; the clinical context and safety profile of this specific head-to-head comparison is therefore less informed by prior literature.,Abstract-only review: complete adverse event data, patient characteristics, baseline pain scores, and analgesic protocol details are unavailable to this reviewer. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ In this double-blind RCT of 126 adults undergoing lower limb fracture surgery, oliceridine PCIA demonstrated non-inferiority to hydromorphone PCIA for resting NRS pain control at 48 hours, with an observed lower rate of PONV in the ITT analysis that was not confirmed in the PP analysis. Oliceridine was associated with a statistically significant but clinically modest reduction in morphine-equivalent consumption. These results are promising but derived from a single center with a 48-hour observation window; multicenter replication with longer follow-up and full adverse-event reporting is needed before practice adoption in this surgical population.