Abstract
BACKGROUND: While propofol remains widely used for endoscopic sedation, its cardiovascular depression and injection pain limitations have prompted exploration of novel agents (remimazolam, ciprofol). This study aimed to compare their safety and efficacy profiles systematically. METHODS: We conducted a network meta-analysis to evaluate remimazolam, ciprofol, and propofol for gastrointestinal endoscopy. Bayesian random-effects models were used to estimate relative risks (RR) and mean differences (MD) with 95% credible intervals(CrI). RESULTS: Forty-two randomized controlled trials (N = 10,540 patients) were included. Remimazolam demonstrated superior cardiovascular safety (RR = 0.44, 95%CrI 0.35-0.54 vs propofol) and lowest respiratory depression risk (RR = 0.36, 0.28-0.46). Propofol showed faster recovery (MD -14.22 min, -2.35 to -30.83 vs remimazolam). Both remimazolam (RR = 0.045) and ciprofol (RR = 0.054) significantly reduced injection pain versus propofol. CONCLUSION: Remimazolam should be prioritized for high-risk patients (cardiovascular/respiratory comorbidities) despite slightly longer recovery times. Propofol remains suitable for low-risk procedures requiring rapid turnover, while ciprofol offers balanced efficacy for endoscopy. TRIAL REGISTRATION: The study was registered with the UK National Institute for Health Research's PROSPERO platform (CRD42024569405; https://www.crd.york.ac.uk/prospero/ ).