Background and Objectives: Remimazolam and remifentanil are ultra-short-acting agents that are used for sedation and analgesia, respectively. Their combined effect on respiratory function is unclear. We evaluated whether co-administration produced dose-dependent respiratory depression and loss of consciousness (LOC) preceded oxygen desaturation. Materials and Methods: A randomized, double-blind trial was conducted from May to July 2024. Female patients (20–65 years; n = 108; American Society of Anesthesiologists physical status I–II) undergoing elective gynecological surgery were selected. Patients received remifentanil via target-controlled infusion (TCI) at effect-site concentrations (Ce) of 1.0, 1.5, or 2.0 ng/mL (Groups 1.0, 1.5, and 2.0) combined with a fixed Ce of 500 ng/mL remimazolam. Respiratory variables, timing of LOC, bispectral index, and adverse events were recorded. Results: Respiratory depression increased in a dose-dependent manner. Jaw thrust was required in 52.8% of Group 1.0 and 91.7% of Group 2.0 (p < 0.001). The need for 100% oxygen increased from 30.6% to 69.4% (p = 0.001). Minute ventilation decreased only in Group 2.0 (p = 0.008). Involuntary movements were frequent in Group 1.0 (p = 0.005). Conclusions: Remimazolam–remifentanil co-administration via TCI induced dose-dependent respiratory depression and pre-LOC desaturation. Therefore, continuous monitoring and careful titration are essential.
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