The ED90 of Oliceridine for Tracheal Intubation in Children: A Biased-Coin Up-and-Down Parallel Dose-Finding Study

Liqun Cheng,1,2 Jing Jiang,1– 3 Mengqi Li,1,2 Yingzhi Dan,1,2 Jijian Zheng,1,2 Yue Huang,1– 3 Kan Zhang1– 3 1Department of Anesthesiology, Shanghai Children’s Medical Center Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China; 2National Children’s Medical Center, Shanghai, 200127, People’s Republic of China; 3Pediatric Clinical Pharmacology Laboratory, Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of ChinaCorrespondence: Kan Zhang, Email drzhangkan@foxmail.com Yue Huang, Department of Anesthesiology Shanghai Children’s Medical Center, affiliated to Shanghai Jiao Tong University School of Medicine & National Children’s Medical Center, No. 1678 Dongfang Road, Shanghai, 200127, People’s Republic of China, Email huangyue@scmc.com.cnBackground: Oliceridine as a novel biased μ-opioid receptors agonist that selectively activates G protein-mediated signaling, has been associated with a lower incidence of opioid-related adverse events (ORAEs). However, the effective dose of oliceridine for tracheal intubation in pediatric anesthesia was unknown.Methods: In this prospective, double-blind, sequential allocation study, 100 children scheduled for general anesthesia were enrolled. An initial intravenous bolus of oliceridine and sufentanil was set at 70 μg/kg and 0.3 μg/kg. Subsequent doses were determined by the response of the previous participant using a biased coin up-and-down design (BCUD). Successful sedation was defined as the changes of hemodynamics was less than 20% of baseline. The 90% effective dose (ED90) and its 95% confidence interval (CI) were estimated, using isotonic regression.Results: For tracheal intubation in children aged 1– 12 years, the ED90 of oliceridine was 74.3 μg/kg (95% CI: 73.6 to 77.4 μg/kg), while that of sufentanil was 0.34 μg/kg (95% CI: 0.32 to 0.42 μg/kg), yielding an equivalent dose ratio of approximately 220:1 (oliceridine: sufentanil). The incidences of hemodynamic changes were comparable between groups before and after tracheal intubation. No hypoxemia was observed after administration of oliceridine and sufentanil. All adverse events were self-limited and no intervention was required.Conclusion: Oliceridine at an ED90 of 74.3 μg/kg can be effectively used for tracheal intubation during pediatric anesthesia.