BACKGROUND: Cipepofol is a highly selective gamma-aminobutyric acid A receptor potentiator. As a new sedative drug, detailed studies on its respiratory effects are further needed. The present study aims to investigate the effects of cipepofol on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients. METHODS: In this one-arm physiological study, cipepofol was initiated at 0.3 mg/kg/h and increased by 0.1 mg/kg/h every 30 min until reaching 0.8 mg/kg/h. Discontinuation criteria were Richmond Agitation and Sedation Scale (RASS) score ≤ -4 or respiratory rate (RR) <
8 breaths/min or pulse oxygen saturation (SpO RESULTS: 20 patients were enrolled and all of them completed the cipepofol infusion rate at 0.3 mg/kg/h, achieving RASS score of -2 to +1. For the primary outcomes, there was a significant reduction in VT (390.9, [356.6-511.0] vs. 451.6 [393.5-565.9], CONCLUSION: Cipepofol demonstrates the capability to achieve RASS score -2 to +1 in mechanically ventilated adult patients. The effect of cipepofol on breathing patterns was a decrease in VT, while changes in RR and V CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT06287138. https://clinicaltrials.gov/study/NCT06287138.