Abstract Rationale Non-invasive ventilation (NIV) remains a cornerstone in managing acute respiratory failure, but it faces challenges related to patient tolerance of devices. Sedatives and analgesics have shown potential benefits in improving NIV compliance. Pairwise meta-analyses lack direct comparisons across agents, thereby limiting the synthesis of evidence. The study aims to compare different agents through conducting a Bayesian network meta-analysis (NMA) that integrates direct and indirect evidence from randomized controlled trials (RCTs). Methods This NMA followed PRISMA guidelines for systematic reviews and NMAs. A comprehensive search was conducted in three databases (Embase, MEDLINE, Cochrane Library) from their inception to September 20, 2025. Risk of bias was assessed using the Cochrane risk-of-bias tool (RoB 2). MetaInsight v6.4.0 was used for data synthesis. Confidence of evidence in Network Meta-Analysis (CINeMA) was used to assess the level of confidence. Results Fifteen out of 17 included RCTs reported the outcome of intubation. After excluding three studies with high risk of bias, twelve studies encompassing 1092 patients were included for network meta-analysis. Compared with placebo, dexmedetomidine demonstrated the strongest evidence for reducing intubation rates (odds ratio OR, 0.3; 95% credible interval CrI, 0.12-0.71). Standard of care, defined as medications used at physician discretion other than dexmedetomidine, ranked second (OR, 0.23; 95% CrI, 0.02-2.69) although it did not reach a statistically significant difference compared to placebo. Its wide credible interval reflected uncertainty due to limited data. Remifentanil (OR, 0.65; 95% CrI, 0.12-3.65) and midazolam (OR, 0.71; 95% CrI, 0.21-2.61) showed moderate but nonsignificant benefits. Haloperidol (OR, 0.83; 95% CrI, 0.13-5.47) was comparable to placebo. Propofol showed a non-statistically significant increase in intubation rate (OR, 3.52; 95% CrI, 0.41-34) and ranked last. The surface under the cumulative ranking curve (SUCRA) confirmed dexmedetomidine as the most effective agent for reducing intubation rates (SUCRA = 85.3%) and propofol as the least effective (SUCRA = 6.4%). The residual deviance scatter plot indicated minimal inconsistency, and per-arm residual deviance showed good model fit. Conclusion The present analysis supports the use of dexmedetomidine in improving NIV compliance and reducing the need for intubation. Other agents, including remifentanil, midazolam, and haloperidol, showed limited evidence of benefit, with uncertainty due to sparse data. Propofol was the least effective and potentially increased the risk of intubation. Further large-scale and high-quality RCTs are needed to establish the comparative efficiency of other sedatives or analgesics. This abstract is funded by: None
Glasgow et al. (Fri,) studied this question.