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.

BACKGROUND

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.