This single-center, prospective, randomized, controlled study was conducted from September 2022 to May 2023 in Union Hospital, Wuhan, China. The Ethics Committee of our hospital approved this study (2022-0539-01). Written informed consent was obtained from legally representatives. The study was registered (ClinicalTrials.gov, NCT05539521).

The inclusion criteria were age between 18 and 80 years, expected to receive mechanical ventilation for longer than 8 h, and the need for intravenous sedative medication for deep sedation, defined as a Richmond Agitation and Sedation Scale (RASS) of − 4 or − 5. The main exclusion criteria were acute severe neurological disorder or coma, systolic blood pressure less than 90 mm Hg after appropriate intravenous volume replacement and vasopressors, and heart rate less than 50 beats/min or second- or third-degree heart block in the absence of a pacemaker (complete list of exclusion criteria in Additional file 1).

Eligible patients were randomized into either group in a 1:1 ratio by opening consecutively numbered, sealed, opaque envelopes with computer-generated allocation. Patients were blinded to allocation, but medical staff were not.

The degree of sedation was measured and recorded every 4 h using RASS. The Narcotrend Index (NI) value was continuously monitored at the same time using Narcotrend-Compact M (MT MonitorTechnik, Germany) and recorded every 4 h.

The remifentanil infusion was started at an initial rate of 6.0 μg/kg/h and titrated to obtain adequate pain control. Patients allocated to the remimazolam group received remimazolam besylate (Yichang Humanwell Pharmaceutical Co., Ltd., China) intravenously at an initial infusion rate of 0.3 mg/kg/h and adjusted (maximum of 3.0 mg/kg/h) to achieve the desired level of sedation. Patients allocated to the propofol group received propofol (Fresenius Kabi China Co., Ltd.) intravenously at an initial infusion rate of 3.0 mg/kg/h and adjusted (maximum of 12.0 mg/kg/h) to achieve the desired level of sedation. If deep sedation was not achieved at the maximum infusion rate, rescue sedation with midazolam was used. The study was continued until one of the following occurred first: 48 h after enrollment, no need for deep sedation, discharge from our ICU, death, or requested cessation by attending physicians or investigators. If a patient still required sedation after stopping the intervention, other sedatives were given at the discretion of attending physicians.

The primary outcome was the percentage of time within the target sedation range without rescue sedation. The secondary outcomes included ventilator-free hours within 7 days, successful extubation (defined as no reintubation or tracheostomy within 48 h after extubation), length of ICU stay, and 28-day mortality. Patients were considered hospitalized for 28 days if died within 28 days. During the study period, occurrence of hypotension (systolic blood pressure below 80 or diastolic blood pressure below 50) and bradycardia (heart rate below 50) were recorded. Bradycardia was treated with medication to increase heart rate, and hypotension was treated with vasopressors.

This pilot study with no sample size estimation conducted was expected to provide data to calculate sample size for further larger sample-sized trials. Normally distributed variables were reported as mean (standard deviation) and analyzed using the Student’s t test, non-normally distributed variables were reported as median (interquartile range) and analyzed using the Mann–Whitney U test, and categorical variables were reported as number (%) and analyzed using the Chi-square test or the Fisher's exact test. We used Kaplan–Meier plot to present the duration of mechanical ventilation from enrollment to 7 days. Statistical analysis was performed using SPSS 26.0 software (IBM SPSS Statistics, Armonk, NY) and GraphPad Prism 8.2.1 (GraphPad Software, San Diego, CA, USA). A p value < 0.05 was considered statistically significant.