Respiratory Depression Following Concomitant Infusion of Remimazolam and Remifentanil Using Targeted Effect-Site Concentrations: A Randomized Controlled Trial

Abstract

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 (C-e) of 1.0, 1.5, or 2.0 ng/mL (Groups 1.0, 1.5, and 2.0) combined with a fixed C-e 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.