Oliceridine versus Conventional Opioids for the Incidence of Respiratory Depression in Patients with Acute Postoperative Pain: A Systematic Review and Meta-Analysis (Preprint)

BACKGROUND Background: Conventional opioids remain widely used for acute postoperative pain but are limited by adverse effects, particularly respiratory depression. Oliceridine (TRV130), a G protein-biased μ-opioid receptor agonist, was developed to provide analgesia with potentially fewer opioid-related respiratory adverse events. However, the comparative respiratory safety of oliceridine and conventional opioids remains uncertain. OBJECTIVE Objective: To compare the incidence of respiratory depression associated with intravenous oliceridine versus conventional opioids in adult surgical patients. METHODS Methods: Web of Science, PubMed, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials comparing intravenous oliceridine with conventional opioids for postoperative analgesia in adults. The primary outcome was respiratory depression. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with the I² statistic. Publication bias was explored using funnel plots, Egger’s test, Begg’s test, and trim-and-fill analysis. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. RESULTS Results: Fourteen randomized controlled trials involving 2,345 participants were included in the systematic review, and 11 studies reporting respiratory depression were included in the meta-analysis. The pooled analysis showed a lower risk of respiratory depression with oliceridine than with conventional opioids, although the difference was not statistically significant (RR 0.794, 95% CI 0.554–1.139; p = 0.185). This corresponded to an estimated relative risk reduction of 20.6%. Heterogeneity was substantial (I² = 70.2%). Leave-one-out analyses did not materially change the direction of the pooled effect. No statistically significant publication bias was detected (Egger’s p = 0.846; Begg’s p = 0.938). CONCLUSIONS Conclusions: In the available randomized evidence, oliceridine was associated with a numerically lower incidence of respiratory depression than conventional opioids, but the difference was not statistically significant. Given the heterogeneity in outcome definitions and treatment protocols across studies, the current evidence remains inconclusive. Larger trials using standardized respiratory safety endpoints are needed.