Oliceridine 20 μg/kg with Propofol Shows Optimal Balance for Painless Gastroscopy, but Registry Discrepancies Raise Questions

A randomized controlled trial by Hu et al, conducted at Dazhou Central Hospital from July to October 2025, compared three doses of the G protein-biased μ-opioid receptor (搜索)搜索该靶点 agonist oliceridine查看药品详情 with sufentanil查看药品详情—each combined with propofol查看药品详情—for sedation during painless gastroscopy. The study identified oliceridine 20 μg/kg as the dose offering the most favorable balance between sedation success and respiratory safety. However, a letter to the editor published in the same journal raises significant methodological concerns that warrant careful consideration before the respiratory safety conclusions are accepted.

Trial Design and Key Findings

The trial enrolled 188 patients randomized equally into four groups: oliceridine查看药品详情 10 μg/kg (Group L), 20 μg/kg (Group M), 30 μg/kg (Group H), or sufentanil查看药品详情 0.1 μg/kg (Group C), all co-administered with propofol查看药品详情 2 mg/kg. The primary outcome was the incidence of respiratory depression (搜索)搜索该疾病, defined as respiratory rate below 8 breaths per minute, respiratory arrest lasting more than 15 seconds, or SpO2 below 90%.

The overall incidence of respiratory depression (搜索)搜索该疾病 was significantly lower in Group L (15.22%) and Group M (17.39%) compared to Group H (46.67%) and Group C (55.32%) (P < 0.05). Respiratory arrest occurred in 13.04%, 15.22%, 42.22%, and 51.06% of Groups L, M, H, and C, respectively, with Groups H and C showing significantly higher rates (P < 0.05). The proportion of patients requiring airway intervention due to SpO2 below 90% was significantly higher in Group C (14.89%) compared to Groups L and M, both of which recorded zero such events (P < 0.05).

Sedation success rate—defined as completion of gastroscopy without supplemental propofol查看药品详情—was significantly higher in Group M (93.48%) than in Group L (71.74%) (P < 0.05). No statistically significant differences were observed among groups for operation time, total propofol consumption, awakening time, or incidence of hypotension.

Respiratory Safety Profile

The authors note that oliceridine查看药品详情-associated respiratory depression (搜索)搜索该疾病 during endoscopy predominantly presents as transient respiratory arrest with rapid spontaneous recovery. Prior pharmacokinetic data indicate that recovery from respiratory depression with oliceridine is approximately five times faster than with morphine. The favorable safety profile—low incidence of respiratory depression and rapid spontaneous recovery—supports oliceridine's suitability for brief procedures such as painless gastroscopy.

A clear dose-dependent relationship emerged: while low and moderate doses demonstrated respiratory safety advantages over sufentanil查看药品详情, the high-dose oliceridine查看药品详情 group (30 μg/kg) exhibited respiratory depression (搜索)搜索该疾病 rates approaching those of the sufentanil control, suggesting progressive saturation of opioid receptors and reduced receptor selectivity at higher doses.

Registry Discrepancies and Methodological Concerns

In a letter to the editor, correspondents identified three critical issues requiring clarification.

First, the prospectively registered outcomes in the Chinese Clinical Trial Registry (ChiCTR2500097246) differ materially from the published report. The registry designates mean arterial pressure, heart rate, and SpO2 as primary outcomes—not respiratory depression (搜索)搜索该疾病. The registry specifies 120 participants with recruitment from March to April 2025 and ASA physical status I–II, whereas the article reports 188 participants recruited from July to October 2025 with ASA I–III. The registry still indicates "not yet recruiting" and states individual participant data would be made publicly available, yet the article provides no repository or dataset. The correspondents invite the authors to provide the dated protocol, statistical analysis plan, and ethics approval for any amendments.

Second, two post-randomization exclusions are noted. One participant in Group M experienced SpO2 below 90% but was excluded because a tight body-shaping garment was considered to have affected the result. Another in Group H was excluded because the procedure exceeded a prespecified 10-minute threshold—a criterion not reported among eligibility criteria. The correspondents observe that including the excluded Group M participant would change the hypoxemia rate from 0/46 to at least 1/47 and respiratory depression (搜索)搜索该疾病 from 8/46 to at least 9/47. The flow diagram states no participant was excluded from analysis despite these omissions.

Third, the correspondents request greater detail on respiratory event ascertainment. Respiratory arrest—reported in 13.04% to 51.06% across groups—appears to drive much of the composite outcome, yet the report does not state whether apnea was detected using capnography, impedance monitoring, or direct observation. All participants received oxygen at 5 L/min, which can delay pulse-oximetric recognition of hypoventilation. The correspondents recommend reporting pairwise risk differences or risk ratios with 95% confidence intervals and multiplicity-adjusted exact P values, consistent with CONSORT Harms guidance.

Clinical Implications

The study provides useful preliminary evidence that moderate-dose oliceridine查看药品详情 (20 μg/kg) with propofol查看药品详情 may offer an improved therapeutic window for painless gastroscopy compared to sufentanil查看药品详情-based regimens. The authors acknowledge limitations including the single-center design, small sample size, and enrollment of predominantly young, healthy adults, noting that dosing regimens may not be appropriate for older adults or patients with hepatic or renal impairment. Resolution of the registry and methodological concerns raised in the correspondence will be essential for the respiratory safety conclusions to be fully accepted by the clinical community.