Abstract
Background
Oliceridine is a novel µ-opioid receptor agonist designed to reduce opioid-related adverse events while maintaining effective analgesia. However, randomized controlled trials comparing oliceridine with conventional opioids, such as sufentanil, have yielded inconsistent results. This systematic review and meta-analysis aims to compare the effects of oliceridine and sufentanil on postoperative nausea and vomiting.
Methods
We searched PubMed, Embase, and the Cochrane Library databases to identify all randomized controlled trials published from the inception through March 14, 2026, that examined the effects of oliceridine and sufentanil on postoperative nausea and vomiting. Data analysis was performed using RevMan 5.4 software. Binary outcomes were analyzed using risk ratios and 95% confidence intervals, while continuous variables were expressed as mean differences. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias Tool.
Results
Ten randomized controlled trials involving 1408 patients met the inclusion criteria. Compared with sufentanil, oliceridine was associated with a lower incidence of postoperative nausea and vomiting (RR = 0.46, 95% CI 0.36–0.58, P < 0.00001), reduced requirement for rescue antiemetics (RR = 0.46, 95% CI 0.26–0.80, P = 0.006), and a lower incidence of respiratory depression (RR = 0.51, 95% CI 0.38–0.70, P < 0.0001). No statistically significant differences were observed between groups in the number of effective activations of the analgesic pump, rescue analgesia, hypotension, bradycardia, and dizziness.
Conclusions
Oliceridine may reduce the risk of postoperative nausea and vomiting and respiratory depression compared with sufentanil while maintaining comparable analgesic efficacy. These findings support the potential role of oliceridine as an alternative opioid for perioperative analgesia.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12871-026-04041-1.
Keywords: Meta-analysis, Nausea and vomiting, Oliceridine, Sufentanil, Systematic review
Introduction
Postoperative nausea and vomiting (PONV) is among the most common complications after anesthesia, affecting approximately one-third of surgical patients [1]. In addition to causing substantial patient discomfort, PONV is associated with delayed recovery, prolonged hospitalization, and increased healthcare utilization [2–4]. Effective prevention of PONV therefore remains a key priority in perioperative care.
Opioids, particularly sufentanil, are widely used for intraoperative and postoperative analgesia because of their potent analgesic efficacy and rapid onset [5]. However, their clinical use is limited by dose-dependent adverse effects, most notably respiratory depression and PONV [6, 7]. Oliceridine is a novel µ-opioid receptor agonist designed to preferentially activate G-protein–mediated signaling while limiting β-arrestin recruitment. This biased signaling profile has been proposed to maintain effective analgesia while reducing opioid-related adverse events [8, 9]. However, evidence from randomized controlled trials comparing oliceridine with conventional opioids, including sufentanil, remains inconclusive [10, 11].
To clarify these uncertainties, we conducted a systematic review and meta-analysis to compare the effects of oliceridine and sufentanil on postoperative nausea and vomiting, with the aim of providing higher-level evidence to inform perioperative analgesic strategies.
Methods
This systematic review adhered to the PRISMA guidelines and current Cochrane Collaboration recommendations. The protocol was registered in the International Prospective Register of Systematic Reviews (Registration Number: CRD420261340849; available at: https://www.crd.york.ac.uk/prospero/#myprospero).
Search strategy
A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted from database inception to March 14, 2026. The search strategy included the terms “oliceridine” and “sufentanil.” Only randomized controlled trials (RCTs) were considered eligible for inclusion. The search strategies for PubMed, EMBASE, and the Cochrane Library are presented in Appendix 1.
Eligibility criteria
Inclusion criteria are as follows: (1) Participants aged ≥ 18 years; (2) Patients undergoing surgery under general anesthesia, either as outpatients or inpatients; (3) Randomized controlled trials comparing oliceridine with sufentanil within the same study.
Exclusion criteria: (1) Studies not published in full text; (2) Review articles; (3) Case reports; (4) Articles published in non–peer-reviewed journals.
Study selection
Two reviewers independently screened the results produced by the search strategy from the selected databases. All potentially eligible citations, based on title and abstract screening alone, had their full-text versions retrieved for a thorough re-evaluation of inclusion criteria. Any disagreements on full-text study inclusion were discussed until a consensus was reached. If a consensus could not be achieved after discussion, a third reviewer was consulted to make the final decision.
Data extraction
Two authors independently extracted data into a pre-designed spreadsheet. Discrepancies were resolved through re-examination or consultation with a third author. If necessary, we will contact the original author within permissible limits to provide relevant experimental data or publicly available data. If the author cannot be reached, an explanation will be provided. A third reviewer cross-checked extracted values against source manuscripts. The extracted information includes: author, year of publication, type of surgery, drug dosage and administration, primary outcomes, and secondary outcomes.
Primary outcomes
Postoperative nausea and vomiting.
Requirement for rescue antiemetics (The administration of intravenous antiemetic medication following clinically significant nausea or vomiting).
Secondary outcomes
Number of effective activations of the analgesic pump.
Rescue analgesia (If the score on the pain at rest numerical rating scale after surgery was ≥ 4 points or the score on the dynamic pain numerical rating scale was ≥ 7 points, and the effect of the analgesic pump was not satisfactory, rescue analgesia will be administered)
-
3.
Hypotension (The definition of hypotension in each primary study was adopted as the definition of hypotension in this study).
-
4.
Bradycardia.
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5.
Respiratory depression.
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6.
Dizziness.
Risk of bias assessment
Two reviewers assessed the risk of bias using the Cochrane Collaboration tool [12], evaluating random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases. Disagreements were resolved through discussion and, if needed, by consulting a third reviewer. When ten or more studies were included in a meta-analysis, publication bias was assessed using Egger’s test in Stata software [13].
Statistical analysis
Statistical analyses were performed using RevMan (version 5.4, Cochrane Collaborative, 2020). For outcomes reported as medians with interquartile ranges, means and standard deviations were calculated using a validated imputation method before meta-analysis. Descriptive statistics were calculated to determine the mean difference (MD) using the random-effects inverse variance method, with results expressed as MD and 95% confidence intervals (CIs). For dichotomous outcomes, meta-analyses were conducted using risk ratio (RR) and the Mantel–Haenszel random-effects method, with results reported as RR and 95% CI. Statistical significance was defined as a P-value of < 0.05.
Heterogeneity among the included studies was assessed using the Q-test and the I² statistic. According to Cochrane guidelines, heterogeneity was categorized as follows: I² < 25% (low), 25–50% (moderate), 50–75% (substantial), and > 75% (high). These criteria determined whether a fixed-effects or random-effects model was applied for the meta-analysis. When I² ≤ 50%, heterogeneity was considered not statistically significant and a fixed-effects model was used. Conversely, when I² > 50%, substantial heterogeneity was observed and a random-effects model was applied.
Results
Results of the literature search
The systematic search identified 47 citations. After removing duplicates, a total of 35 citations were screened, with 11 excluded for not being randomized controlled trials. 11 citations were excluded following the title and abstract review. Two study [11, 14] was excluded due to unavailable full text, and a study [15] excluded because it was a retrospective study. Ultimately, 10 studies met the inclusion criteria and were included in the meta-analysis (Fig. 1).
Fig. 1.
Study flow diagram
Study characteristics
The characteristics of the included RCTs are summarized in Table 1.
Table 1.
Characteristics of the included studies
| Author, Year | Groups(n) | Age (Years) | Surgery | Drug dosage and administration | |
|---|---|---|---|---|---|
| Sufentanil | Oliceridine | ||||
| Baoyu Ma 2025 [16] |
sufentanil (307) oliceridine (305) |
54 ± 13 53 ± 12 |
Elective gastroscopy combined with colonoscopy examination | 5–7.5 µg of sufentanil administered intravenously. | 1 or 1.5 mg of oliceridine administered intravenously. |
| Jinjuan Duan 2026 [17] |
sufentanil (40) oliceridine (40) |
49.38 ± 5.43 51.00 ± 5.53 |
Elective total laparoscopy hysterectomy |
Following laparoscopic resection, patients received an intravenous loading dose of 0.2 µg/kg of sufentanil, followed by 2 µg/kg sufentanil of oliceridine administered via patient-controlled analgesia. |
Following laparoscopic resection, patients received an intravenous loading dose of 0.05 mg/kg of oliceridine, followed by 0.35 mg/kg of oliceridine administered via patient-controlled Analgesia. |
| Lin Kexin 2024 [18] |
sufentanil (60) oliceridine (60) |
52.5 ± 1.5 54.3 ± 1.4 |
Undergoing breast-conserving surgery | Administer 15 µg of sufentanil intravenously during induction of anesthesia. Administer 15 µg of sufentanil intravenously 2 min before skin incision. Postoperatively, 50 µg of sufentanil was administered via patient-controlled intravenous analgesia. |
Administer 3 mg of oliceridine intravenously during induction of anesthesia. Administer 3 mg of oliceridine intravenously 2 min before skin incision. Postoperatively, 10 mg of oliceridine was administered via patient-controlled intravenous analgesia. |
| Lvlv Chen 2025 [19] |
sufentanil (40) oliceridine (40) |
67.6 ± 2.4 68.4 ± 2.7 |
Elderly patients with hypertension | Induction with sufentanil 0.3 µg·kg− ¹. | Induction with oliceridine 0.04 mg·kg− ¹. |
| Qiu Jia 2025 [20] |
sufentanil (32) oliceridine (30) |
46.5 ± 15.0 47.2 ± 11.1 |
Painless endoscopy | 0.1 µg/kg of sufentanil administered intravenously. | 0.02 mg/kg of oliceridine administered intravenously. |
| Sun Yalin 2024 [21] |
sufentanil (35) oliceridine (35) |
51 ± 12 51 ± 10 |
Elective bone tumor resection | 2 µg/kg sufentanil administered via patient-controlled intravenous analgesia. |
0.4 mg/kg oliceridine administered via patient-controlled intravenous analgesia. |
| Yifu Tian 2025 [22] |
sufentanil (36) oliceridine (37) |
65.6 ± 3.7 65.3 ± 4.4 |
Patients undergoing laparoscopic radical resection for rectal cancer | 2 µg/kg sufentanil administered via patient-controlled intravenous analgesia. |
0.35 mg/kg oliceridine administered via patient-controlled intravenous analgesia. |
| Yuxiang Meng 2025 [10] |
sufentanil (65) oliceridine (65) |
56.3 ± 7.4 55.5 ± 6.3 |
Elective thoracoscopic surgery | 2 µg/kg sufentanil administered via patient-controlled intravenous analgesia. |
0.4 mg/kg oliceridine administered via patient-controlled intravenous analgesia. |
| Zhou Yi 2024 [23] |
sufentanil (40) oliceridine (40) |
41 ± 13 47 ± 11 |
Patients with thyroid cancer undergoing radical surgery | Administer 15 µg of sufentanil intravenously during induction of anesthesia. If, within 3 min of endotracheal intubation, the mean arterial pressure or heart rate increases by more than 20% above baseline, administer an additional 5 µg of sufentanil. Administer 15 µg of sufentanil intravenously 2 min before skin incision. |
Administer 3 mg of oliceridine intravenously during induction of anesthesia. If, within 3 min of endotracheal intubation, the mean arterial pressure or heart rate increases by more than 20% above baseline, administer an additional 1 mg of oliceridine. Administer 3 mg of oliceridine intravenously 2 min before skin incision. |
| Zongxing Ke 2025 [24] |
sufentanil (50) oliceridine (51) |
44.9 ± 5.7 41.7 ± 7.4 |
hysteroscopic surgery | 5 µg of intravenous sufentanil. | 1 mg of intravenous oliceridine. |
Quality assessment
Risk of bias assessments for the included studies is presented in Fig. 2. All studies described their methods of randomization, and 5 studies described their methods of allocation concealment. All studies had a low risk of bias for blinding of participants and personnel. Blinding of outcome assessment was rated as low risk in nine studies. Additionally, 7 studies were deemed to have adequately reported all predefined outcomes. However, low publication quality in some studies contributed to potential bias [23].
Fig. 2.
Risk of bias summary
Primary outcomes
Postoperative nausea and vomiting
Ten studies [10, 16–24] involving 1408 participants reported the incidence of postoperative nausea and vomiting. Pooled analysis showed that oliceridine was associated with a lower incidence of nausea and vomiting compared with sufentanil (RR = 0.46, 95% CI 0.36–0.58, P < 0.00001, I² = 0%) (Fig. 3A).
Fig. 3.
A Subgroup analysis of postoperative nausea and vomiting according to patient age. B Subgroup analysis of postoperative nausea and vomiting according to drug dose. C Subgroup analysis of postoperative nausea and vomiting based on the timing of administration. D Sensitivity analysis of postoperative nausea and vomiting. E Funnel plot and Egger’s test
Subgroup analyses yielded consistent findings. When stratified by patient age, both elderly patients (≥ 60 years) and adults (≥ 18 years) showed a lower incidence of nausea and vomiting in the oliceridine group (Fig. 3A). When stratified by drug dose, the incidence of nausea and vomiting remained lower in the oliceridine group regardless of whether a low or high dose was administered (Fig. 3B). Similarly, subgroup analysis based on the timing of administration demonstrated a lower incidence of nausea and vomiting with oliceridine both when administered intraoperatively via intravenous injection and when delivered postoperatively through patient-controlled analgesia (Fig. 3C).
Sensitivity analysis indicated that the results of this meta-analysis did not change significantly with variations in the number of included studies, suggesting that the findings were robust (Fig. 3D).
However, the Egger’s test (P = 0.016) and the funnel plot suggested the presence of potential publication bias (Fig. 3E).
Rescue antiemetics
Three studies [10, 16, 21] involving 812 participants reported the use of rescue antiemetics. Pooled analysis demonstrated that oliceridine was associated with a lower requirement for rescue antiemetics compared with sufentanil (RR = 0.46, 95% CI 0.26–0.80, P = 0.006, I² = 5%) (Fig. 4).
Fig. 4.
Forest plots of incidence of rescue antiemetics
Secondary outcomes
Number of effective activations of the analgesic pump.
Three studies [18, 21, 22] involving 263 participants reported the number of effective activations of the analgesic pump. The pooled analysis showed no statistically significant difference between the two groups (MD = -0.06, 95% CI -0.82–0.71, P = 0.89, I² = 75%) (Fig. 5A). Subsequently, a sensitivity analysis was performed by excluding the study conducted by Sun et al. [21], which resulted in a reduction in heterogeneity (MD = 0.23; 95% CI -0.14–0.59, P = 0.22, I2 = 29%) (Fig. 5B). Due to the limited number of included studies, no subgroup analysis was performed.
Fig. 5.
A Forest plot of number of effective activations of the analgesic pump. B Sensitivity analysis of number of effective activations of the analgesic pump
Rescue analgesia
Five studies [10, 17, 18, 21, 22] involving 473 participants reported the incidence of rescue analgesia. The pooled analysis indicated no significant difference between the oliceridine and sufentanil groups (RR = 1.12, 95% CI 0.76–1.64, P = 0.56, I² = 31%) (Fig. 6).
Fig. 6.
Forest plot of the incidence of rescue analgesia
Hypotension
Six studies [10, 16, 19, 20, 23, 24] involving 1065 participants reported the incidence of hypotension. There was no statistically significant difference between the two groups (RR = 0.82, 95% CI 0.65–1.04, P = 0.11, I² = 35%) (Fig. 7).
Fig. 7.
Forest plots of incidence of hypotension
Bradycardia
Four studies [10, 16, 23, 24] involving 923 participants reported the incidence of bradycardia. The pooled analysis showed no statistically significant difference between the two groups (RR = 0.77, 95% CI 0.53–1.12, P = 0.17, I² = 42%) (Fig. 8).
Fig. 8.
Forest plots of incidence of bradycardia
Respiratory depression
Nine studies [10, 16–18, 20–24] involving 1328 participants reported the incidence of respiratory depression. The pooled analysis showed a lower incidence of respiratory depression in the oliceridine group compared with the sufentanil group (RR = 0.51, 95% CI 0.38–0.70, P < 0.0001, I² = 0%) (Fig. 9).
Fig. 9.
Forest plots of incidence of respiratory depression
Dizziness
Five studies [10, 17, 18, 20, 23] involving 472 participants reported the incidence of dizziness. No statistically significant difference was observed between the two groups (RR = 0.78, 95% CI 0.51–1.19, P = 0.25, I² = 0%) (Fig. 10).
Fig. 10.
Forest plots of incidence of dizziness
Discussion
In this meta-analysis, we found that compared with sufentanil, oliceridine reduces the incidence of nausea and vomiting, the use of rescue antiemetics, and the incidence of respiratory depression, while providing analgesic effects comparable to those of sufentanil. Taken together, these findings suggest that oliceridine may represent a potential alternative opioid strategy for perioperative analgesia, particularly for patients at elevated risk of opioid-related adverse events.
Nausea and vomiting are the most common postoperative symptoms in patients, and their occurrence is associated with various factors, including the type of surgery, duration of surgery, anesthetic agents and techniques, and preoperative anxiety [25]. This study found that the incidence of nausea and vomiting was significantly higher with sufentanil than with oliceridine (24.0% vs. 11.0%), and the rate of requiring emergency antiemetic treatment was also higher with sufentanil. This is because oliceridine reduces the recruitment of β-arrestin, thereby decreasing β-arrestin-mediated gastrointestinal adverse reactions and accelerating the recovery of intestinal function [26, 27]. Furthermore, our subgroup analysis based on age, drug dose, and timing of administration showed that, regardless of whether the patients were elderly or adults, whether low or high doses were used, or whether the drug was administered intravenously during surgery or via postoperative patient-controlled analgesia, oliceridine consistently reduced the incidence of nausea and vomiting, suggesting that this conclusion is highly robust and universally applicable.
As a novel opioid, oliceridine exerts its analgesic effects by stimulating G protein-coupled pathways. Our study found no statistically significant difference in the number of effective PCIA presses or the rescue analgesia rate between sufentanil and oliceridine. This indicates that oliceridine provides potent analgesia comparable to that of traditional opioids; its mechanism is attributed to the selective activation of G protein-coupled signaling pathways, thereby achieving analgesic effects similar to those of sufentanil [28–30].
Opioid-induced respiratory depression is one of the most serious complications associated with opioid therapy and, in severe cases, may lead to apnea or even death [31]. Therefore, we strive to minimize the occurrence of respiratory depression when administering opioids. This study found that the incidence of respiratory depression was higher with sufentanil than with oliceridine (15.3% vs. 7.7%). This result is consistent with previous reports, suggesting that oliceridine may offer a potential advantage over traditional opioids in reducing respiratory depression. Although the incidence of dizziness, hypotension, and bradycardia was lower with oliceridine, these differences were not statistically significant, which may be related to the small sample size.
Although this meta-analysis has several strengths, several limitations should be acknowledged. First, all included studies were conducted in China, which may limit the generalizability of the results to other populations and healthcare systems. Differences in patient characteristics, perioperative management practices, and healthcare settings may influence the applicability of these findings beyond the Chinese context.
Second, all eligible studies compared oliceridine with sufentanil, a commonly used perioperative opioid in China. Therefore, the present findings should be interpreted within the context of this specific comparator. Notably, the pivotal phase III APOLLO-1 and APOLLO-2 trials that supported the regulatory approval of oliceridine compared oliceridine with morphine rather than sufentanil. Given the substantial differences between morphine and sufentanil in pharmacokinetic properties, receptor-binding characteristics, and clinical applications, the results of the present meta-analysis cannot be directly extrapolated to comparisons involving morphine, fentanyl, other opioids commonly used in Western perioperative practice. Third, a substantial proportion of the included studies were published in a single regional journal, which may increase the risk of publication or selective-reporting bias. Although no major concerns were identified during study appraisal, the possibility of an overestimation of treatment effects cannot be entirely excluded. Fourth, clinical heterogeneity was present across the included trials. Variations in surgical procedures, anesthetic techniques, perioperative antiemetic strategies, and dosing regimens of both oliceridine and sufentanil may have contributed to differences in treatment effects and influenced the pooled estimates. Finally, five included studies reported inadequate allocation concealment, which may have introduced selection bias and affected the internal validity of the pooled results. Consequently, the findings should be interpreted with appropriate caution. Future large-scale, multicenter, rigorously designed randomized controlled trials involving diverse patient populations are needed to further establish the efficacy and safety profile of oliceridine in perioperative pain management.
Conclusion
In this systematic review and meta-analysis of randomized controlled trials involving patients undergoing surgery under general anesthesia, oliceridine was associated with a significantly lower incidence of postoperative nausea and vomiting and reduced use of rescue antiemetics compared with sufentanil, while providing comparable analgesic efficacy. In addition, the incidence of respiratory depression appeared to be lower among patients receiving oliceridine.
These findings suggest that oliceridine may represent a promising alternative opioid strategy for perioperative analgesia, particularly in patients at elevated risk of opioid-related adverse events.
Supplementary Information
Acknowledgements
Not applicable.
Authors’ contributions
Jixiang Wan, Jiaman Li, and Fangjun Wang contributed to the study design, data collection, statistical analysis, and manuscript preparation. Li Liao, Chunyang Shao, and Li Zhao assisted with data collection and statistical analysis. All authors reviewed and approved the final manuscript.
Funding
None.
Data availability
All data generated or analyzed during this study are included in the manuscript.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Data Availability Statement
All data generated or analyzed during this study are included in the manuscript.