Pharmacological agents for procedural sedation and analgesia in patients undergoing gastrointestinal endoscopy: a systematic review and network meta-analysis.

Background: Procedural sedation and analgesia is crucial for gastrointestinal endoscopy to improve patient comfort and facilitate procedural success. However, pharmacological agents differ in their efficacy and safety profiles, and the optimal agent to balance these outcomes remains uncertain, creating challenges in clinical decision-making. Therefore, we conducted a network meta-analysis to comprehensively evaluate and compare the efficacy and safety of various pharmacological agents. Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 10, 2025. Randomised controlled trials (RCTs) comparing at least two intravenous pharmacological agents in adult patients undergoing gastrointestinal endoscopy were included. Evidence quality was assessed using the Cochrane Risk of Bias 2.0 tool. Efficacy outcomes included sedation success rate and induction time; safety outcomes included time to full alertness, recovery time, and adverse events (hypoxia, hypotension, bradycardia, and postoperative nausea and vomiting [PONV]). A random-effects network meta-analysis was performed. Risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes were calculated, with 95% confidence intervals (CIs). Treatment rankings were presented using surface under the cumulative ranking (SUCRA) curves. The study protocol was registered with PROSPERO (CRD42024572207). Findings: The network meta-analysis included 152 RCTs with 26,527 patients, evaluating 37 interventions. No regimen demonstrated statistically significant superiority over propofol-opioids in terms of sedation success, which remained the reference standard. However, Etomidate-opioids achieved the highest SUCRA ranking for sedation success (SUCRA = 84.5%) and performed favorably in bradycardia (SUCRA = 79.4%), time to full alertness (SUCRA = 65.3%), and recovery time (SUCRA = 82.8%). Notably, etomidate-opioids significantly reduced the risk of hypoxia compared with propofol-opioids (RR = 0.35, 95% CI 0.16, 0.79; SUCRA = 55.0%), but showed no significant differences in hypotension (SUCRA = 45.5%), bradycardia (SUCRA = 79.4%), time to full alertness (SUCRA = 65.3%), or recovery time (SUCRA = 82.8%). It was, however, associated with an increased the risk of PONV (RR = 2.61, 95% CI 1.13, 6.07, SUCRA = 29.4%). Esketamine-remimazolam demonstrated an excellent safety profile, significantly reducing the risk of hypotension (RR = 0.12, 95% CI 0.06, 0.27; SUCRA = 95.6%) and bradycardia (RR = 0.19, 95% CI 0.06, 0.55; SUCRA = 88.3%) and shortening time to full alertness compared with propofol-opioids (MD = -6.05 min, 95% CI -11.85, -0.24; SUCRA = 92.7%). However, its SUCRA ranking for sedation success was lower than that of etomidate-opioids (63.4% vs. 84.5%), with no statistically significant difference observed between esketamine-remimazolam and etomidate-opioids (RR = 1.29, 95% CI 0.68, 2.45). Interpretation: Although no pharmacological regimen demonstrates superior sedation success compared with propofol-opioids, which serve as the standard comparator, etomidate-opioids regimens offer a favorable balance between sedation efficacy and safety, though they warrant attention due to an increased risk of PONV. Esketamine-remimazolam demonstrates superior hemodynamic stability and faster recovery but may be less effective in achieving sedation success. Midazolam-based regimens demonstrate lower efficacy and prolonged recovery and are therefore not recommended. Funding: None.