Nausea and vomiting as adverse events of oliceridine: a systematic review and meta-analysis of randomized controlled trials

Background: Postoperative nausea and vomiting (PONV) continue to be some of the most common and troublesome complications following anesthesia. Oliceridine, a G protein-biased µ-opioid receptor agonist, has the potential to provide effective pain relief while reducing the incidence of opioid-associated side effects. Objectives: The aim of this study is to evaluate the effectiveness and safety of oliceridine for preventing PONV compared with morphine and a placebo. Methods: A comprehensive search was performed across PubMed/MEDLINE, Embase (Ovid), and the Cochrane Central Register of Controlled Trials (CENTRAL) from their inception up to 30 September 2025, without any language limitations. Randomized controlled trials (RCTs) comparing oliceridine with morphine or placebo were included. Outcomes included incidence of nausea, vomiting, and other opioid-related adverse events (ORAEs). Pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. Results: This meta-analysis included five studies, with a total of 1,767 patients. The pooled analysis showed that oliceridine significantly reduced the incidence of postoperative nausea compared with morphine (risk ratio [RR] = 0.80; 95% confidence interval [CI] = 0.70-0.90). In dose-specific analyses, the RRs were 0.58 (95% CI = 0.50-0.67) for the 0.1 mg group, 0.82 (95% CI = 0.74-0.92) for the 0.35 mg group, and 1.00 (95% CI = 0.91-1.11) for the 0.5 mg group. Oliceridine also decreased the risk of postoperative vomiting (RR = 0.55; 95% CI = 0.45-0.67) relative to morphine. Subgroup analyses yielded RRs of 0.39 (95% CI = 0.31-0.50), 0.54 (95% CI = 0.38-0.78), and 0.80 (95% CI = 0.68-0.95) for the 0.1 mg, 0.35 mg, and 0.5 mg groups, respectively. Moreover, oliceridine appeared to lower the incidence of opioid-related adverse events, including dizziness (RR = 0.89; 95% CI = 0.76-1.04), dry mouth (RR = 0.50; 95% CI = 0.37-0.69), pruritus (RR = 0.50; 95% CI = 0.35-0.70), and somnolence (RR = 0.61; 95% CI = 0.45-0.82). Based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, the certainty of evidence ranged from moderate to low. Conclusion: Oliceridine, particularly at 0.1-0.35 mg demand doses, reduces PONV and several opioid-related adverse events compared with morphine while maintaining effective analgesia. However, compared with placebo, typical opioid adverse effects remain. Further large-scale RCTs are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024604703, identifier PROSPERO (CRD42024604703).