Intraosseous versus intravenous vascular access in adults with out-of-hospital cardiac arrest: a meta-analysis with trial sequential analysis and meta-regression analysis.

Establishing vascular access during cardiopulmonary resuscitation is essential for delivering guideline-recommended medications. This meta-analysis aims to compare the clinical effectiveness of initial vascular access attempts through the intraosseous route to the intravenous route in patients with out-of-hospital cardiac arrest (OHCA). A comprehensive literature search was conducted across PubMed, Cochrane, Scopus, and Web of Science, up to March 2025, for randomized controlled trials (RCTs) and propensity score-matched (PSM) observational studies comparing initial attempt intraosseous access with initial intravenous access in patients with OHCA. R Studio version 4.4.2 was used to perform statistical analysis applying a random-effect model. Trial sequential analysis (TSA) was conducted to determine the robustness of findings and estimate required information size (RIS). Four RCTs and four PSM studies involving 28 632 patients with OHCA were identified. The analysis revealed no significant differences between initial vascular access attempts via the intraosseous route compared with the intravenous route regarding survival to hospital discharge [odds ratio (OR): 0.94, 95% confidence interval (CI): 0.77-1.13, P  = 0.49], sustained return of spontaneous circulation (OR: 0.87; 95% CI: 0.74-1.02, P  = 0.09) or survival with favorable neurological outcomes (OR: 0.74, 95% CI: 0.54-1.03, P  = 0.08). Meta-regression identified initial shockable rhythm as a significant modifier of survival to hospital discharge ( P  = 0.012). TSA demonstrated the Z curve failed to reach the RIS, indicating that further studies are needed for conclusive evidence. In adults with OHCA, establishing vascular access through the intraosseous route demonstrates comparable effects to intravenous access in terms of survival and neurological outcomes. Further RCTs are needed to strengthen the evidence base and should assess long-term effects, promote protocol standardization, and enhance paramedic training.