Comparative long-term sedation efficacy of remimazolam vs propofol in malignant patients with mechanical ventilation: an exploratory non-inferiority randomized study

Abstract Enhanced comfort and effective sedation are essential for mechanically ventilated patients, particularly in the ICU. This study evaluates the safety and effectiveness of remimazolam, a novel ultra-short-acting benzodiazepine, compared to propofol in this patient population. A randomized controlled trial was conducted on patients with malignancy aged 18–80 years requiring mechanical ventilation for over 24 h in the ICU of the Cancer Hospital of the Chinese Academy of Medical Sciences from June 2022 to May 2025. The trial was registered prior to patient recruitment at chictr.org.cn (ChiCTR2200058409). Patients received either remimazolam or propofol with regular analgesia. The primary outcome was the ability to maintain light sedation as measured by the Richmond Agitation-Sedation Scale (RASS: from-2 to + 1). Compared to propofol, if remimazolam achieves a proportion of patients maintaining light sedation that is not less than 10% at 6-, 24-, and 48 h, we will consider this indicative of noninferiority. Secondary outcomes included 7-day extubation rates, ICU length of stay, 28-day survival rates, the proportion of patients requiring adjunctive sedation, incidence of adverse events such as hypotension and delirium, and inflammatory response indicators. A total of 110 patients were enrolled (55 remimazolam, 55 propofol). Baseline characteristics were comparable. Both sedation methods achieved comparable success in reaching target sedation levels at 6-, 24- and 48-hour post-initiation of sedation (difference >-10%, P for noninferiority testing < 0.05). Extubation rates at 7 days were similar (78.3% for remimazolam vs. 76.5% for propofol, p = 0.866) and the median ICU length of stay did not differ significantly (8.2 days for remimazolam vs. 7.3 days for propofol, p = 0.546). Survival rates at 28 days were high and similar for both groups (98.2%, p = 1.000). Both groups required dexmedetomidine for adjunctive sedation (9.1% vs. 10.9%, p = 1.000). Adverse events were also comparable. Notably, the remimazolam group showed a lower neutrophil-to-lymphocyte ratio at 24 and 48 h compared to the propofol group (p = 0.048 and p = 0.046, respectively). Remimazolam offers comparable effectiveness and safety to propofol for sedation in mechanically ventilated ICU patients with malignancy.