Adjunctive Oliceridine During Propofol or Ciprofol Sedation for Same-Session Bidirectional Endoscopy in Older Adults: A Multicenter Randomized 2×2 Factorial Trial

Yongjiu Ji,1,2,* Chenxi Xu,2,* Siqi Yang,2 Qin Wang,1 Weibing Zhao,1 Jian Yu,3 Zheng Gu,4 Ning Qian,5 Xiaolin Yang,6 Shaowen Tang,7 Zifeng Wu,2 Chun Yang21Department of Anesthesiology, The Fifth People’s Hospital of Huai’an, Huai’an, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Anesthesiology, Taixing People’s Hospital, Taixing, People’s Republic of China; 4Department of Anesthesiology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, People’s Republic of China; 5Department of Anesthesiology, Taizhou Second People’s Hospital, Taizhou, People’s Republic of China; 6Department of Anesthesiology, The People’s Hospital of Rugao, Rugao, People’s Republic of China; 7Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun Yang; Zifeng Wu, Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Email chunyang@njmu.edu.cn; zifengwu57@126.comPurpose: We evaluated adjunctive oliceridine with propofol or ciprofol in older adults undergoing same-session bidirectional endoscopy.Patients and Methods: In this multicenter, double-blind, placebo-controlled 2× 2 factorial trial, 360 adults aged 65– 80 years were randomized 1:1:1:1 to oliceridine or saline placebo with propofol or ciprofol. The primary outcome was time from completion of the initial sedative dose to the first Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score of 5, confirmed by two subsequent scores of 5 at 1-min intervals. Main-effect comparisons were prespecified; interaction and simple-effect analyses were exploratory because the trial was not powered for interaction testing.Results: The primary analysis included 357 participants. Estimated marginal mean differences in awakening time were − 1.42 min for oliceridine versus placebo (95% CI − 2.43 to − 0.40, P = 0.007) and − 1.84 min for propofol versus ciprofol (95% CI − 2.85 to − 0.82, P < 0.001); the latter was smaller than the prespecified 3-min clinically important difference. In the post hoc final-dose analysis, the oliceridine–placebo difference was 0.09 min (95% CI − 0.78 to 0.96, P = 0.833). Exploratory interaction analysis suggested a greater oliceridine effect with ciprofol. Oliceridine reduced supplemental sedative use (risk difference − 16.7%, 95% CI − 24.8% to − 8.5%, adjusted P < 0.001) and shortened time to discharge readiness (difference − 1.64 min, 95% CI − 2.30 to − 0.99, adjusted P < 0.001), but increased hypotension (risk difference 15.6%, 95% CI 7.6% to 23.6%, P < 0.001).Conclusion: Adjunctive oliceridine reduced supplemental sedative use and modestly shortened the prespecified overall awakening interval, but the awakening difference was not evident when timed from the final sedative dose, and hypotension increased. Propofol modestly shortened awakening versus ciprofol. The apparently greater oliceridine effect with ciprofol was exploratory and hypothesis-generating.Trial Registration: Chinese Clinical Trial Registry, ChiCTR2500110992.Keywords: oliceridine, propofol, ciprofol, deep sedation, gastrointestinal endoscopy