Determination of ED50 and ED95 for Ciprofol in Morbidly Obese Patients During Induction of General Anesthesia: A Single-Center, Up-and-Down Study Based on Lean Body Weight

Chao-min Wu, Ji-min Wu, Jian-xin Jiang, Qiao min Xu, Xue-hao Han, Gong-chen Duan Department of Anesthesiology, Lishui People’s Hospital, The First Affiliated Hospital of Lishui University, Wenzhou Medical University Lishui Hospital, Lishui, People’s Republic of ChinaCorrespondence: Gong-chen Duan, Department of Anesthesiology, Lishui People’s Hospital, The First Affiliated Hospital of Lishui University, Wenzhou Medical University Lishui Hospital, No. 1188, Liyang Street, Lishui, Zhejiang, 323000, People’s Republic of China, Tel/Fax +8618957093030, Email 981225178@qq.comBackground: Obesity alters the pharmacokinetics and pharmacodynamics of hypnotic agents; however, dose-finding data for ciprofol during the induction of general anesthesia in morbidly obese adults remain limited. We estimated the lean body weight (LBW)-scaled 50% effective dose (ED50) and 95% effective dose (ED95) of ciprofol for loss of consciousness by using an up‑and‑down sequential design.Methods: This prospective single-center trial enrolled adults aged 18– 65 years with morbid obesity who underwent elective surgery. Ciprofol was administered as a slow intravenous bolus at an initial dose of 0.76 mg kg− 1 (LBW), followed by an up‑and‑down algorithm with an adjacent dose ratio of 1.1. Primary outcome: LBW-scaled ED50 and ED95 of ciprofol for loss of consciousness. ED50 and ED95 values were estimated using probit analysis. Hemodynamics and adverse events were collected as pre-specified secondary endpoints.Results: Thirty-six patients were included in the study. The sequence yielded either successful or failed crossovers. The LBW-scaled ED50 and ED95 of ciprofol for loss of consciousness were 0.492 mg kg− 1 (95% CI 0.453– 0.531) and 0.634 mg kg− 1 (95% CI 0.524– 0.744), respectively. The mean arterial pressure and heart rate decreased after induction, reaching a nadir approximately 5 min after tracheal intubation, and generally remained ≥ 70% of baseline for most patients. In exploratory, post hoc comparisons of response-defined groups, the incidence of hypotension (37% vs 41%, p=0.79), bradycardia (5% vs 6%, p=0.94), and tachycardia (26% vs 35%, p=0.27) was similar. No other adverse events were reported.Conclusion: The LBW-scaled ED50 and ED95 of ciprofol for loss of consciousness during the induction of general anesthesia in morbidly obese adults were 0.492 and 0.634 mg kg− 1, respectively. Hemodynamics were generally well controlled and adverse events were infrequent.Keywords: ciprofol, morbidly obese, anesthesia induction, 50% effective dose, 95% effective dose