Cardiac arrest outside the hospital is a medical emergency with an alarmingly low survival rate. This event affects millions of people around the world, imposing a considerable burden on health systems due to the high costs of pre-hospital care, prolonged hospitalization, and the need for neurological rehabilitation for most survivors.¹ Studies show that the effectiveness of pre-hospital care and intervention agility are directly associated with the chance of spontaneous circulation (ROSC) return and favorable neurological results.²

Vascular access is fundamental in the management of out-of-hospital cardiac arrest (OHCA). Currently, intravenous (IV) access is often the first choice method used for drug administration during cardiorespiratory resuscitation.³ However, its use may be limited in situations where its implementation is challenging and can result in delays in care and potential complications.⁴ In these cases, the use of intraosseous (IO) access is seen as a viable option due to its speed and ease of administering drugs directly into the bone marrow, making it promising for critical management scenarios in emergency contexts.⁵

However, uncertainties persist regarding the comparability of IO and IV routes in terms of effectiveness in improving return of spontaneous circulation (ROSC) and neurological outcomes. While some studies suggest that IO access may represent a promising alternative when IV access is not feasible, the available evidence remains inconclusive, particularly in critical scenarios such as OHCA.⁶ These limitations hinder the acceptance of IO as an equivalent option to IV, highlighting the need for further research to confirm its role in emergency vascular access.

This meta-analysis aims to synthesize the best available evidence on the effectiveness of IO versus IV access in patients who experienced OHCA and to inform and enhance clinical decision-making.

This meta-analysis was conducted and reported in accordance with the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines.^7,8 It is also registered in PROSPERO under registration number CRD42024609147. Modifications to that protocol are described in Supplementary Appendix 1.

OHCA is a public health emergency, with survival outcomes heavily reliant on the speed and quality of prehospital care. Efficient drug administration is critical to restoring circulation and preventing irreversible brain damage.^17,18 Early intervention, including cardiopulmonary resuscitation and defibrillation, is essential, as each minute without action reduces the likelihood of survival by approximately 10%.^19,20 In this context, vascular access for drug delivery plays a pivotal role in patient management.

Currently, IV access is considered the gold standard due to its efficacy in drug delivery, which contributes to the return of spontaneous circulation and hospital survival.⁶ However, IO access has emerged as a viable alternative in emergencies where IV access is difficult or time-consuming. While IO access has proven effective in many scenarios, uncertainties remain regarding its comparison with IV access, particularly regarding pharmacokinetics, absorption, and its impact on clinical outcomes such as survival and neurological function.^1,21,22

Studies suggest that drug distribution via IO access may be impaired in cases of low circulatory perfusion, while IV access allows for more efficient distribution.²³ However, IO access has the advantage of being faster, especially when IV access is unfeasible.²⁴ Furthermore, the choice between the two methods may depend on the access site (tibia or humerus), with the humerus being more effective for drug distribution.²⁵

The findings from the PARAMEDIC-3 and Reades et al.¹² studies contribute significantly to understanding vascular access strategies during OHCA. PARAMEDIC-3 demonstrated that IO and IV access had similar survival and neurological outcomes, but IO was associated with a lower ROSC rate.¹⁵ On the other hand, Reades et al. showed that tibial IO access offers clear advantages over IV and humerus IO, with higher first-attempt success (91%) and shorter time to access (4.6 minutes).¹² These differences highlight that while IO is effective and rapid in emergencies, the choice of insertion site and the provider's experience play crucial roles in the success of the procedure.

Our meta-analysis, comprising 3 studies and 9,119 patients, compared the effects of IO and IV access in OHCA. The results showed that both methods yielded similar outcomes in terms of survival, favorable neurological outcomes, hospital discharge survival, ROSC, and sustained ROSC, as shown in the central figure. These findings suggest that IO access is equivalent to IV access in terms of clinical outcomes, allowing physicians to make decisions based on clinical circumstances, such as vascular access feasibility or available time.

An important consideration when interpreting ROSC findings is the lack of a uniform definition across the included trials. In the PARAMEDIC-3 trial, ROSC was defined as any return of spontaneous circulation after randomization, regardless of its duration. In contrast, the IVIO trial required ROSC to be sustained for at least 20 minutes, while the VICTOR trial used an even more restrictive definition, requiring circulation to be maintained for at least two hours. This variability in operational definitions likely contributed to the heterogeneity observed in the pooled analysis. In fact, our leave-one-out sensitivity analysis showed that heterogeneity decreased to 0% when the PARAMEDIC-3 trial was excluded, underscoring its influence on study-level variability.

Subgroup analyses showed no significant difference between IO and IV groups in patients with shockable and non-shockable initial rhythms, as well as with or without bystander-performed CPR. These results reinforce the equivalence between the approaches, highlighting the flexibility in choosing the access method based on patient conditions and healthcare provider availability. In critical scenarios, this flexibility can be crucial for patient survival.

Therefore, our meta-analysis indicates that while IV access remains the standard in many protocols, IO access provides an effective alternative, particularly in challenging situations.

Finally, cost-effectiveness and applicability in different healthcare contexts should be considered. Most of the trials included were conducted in high-income countries with well-established and advanced prehospital emergency systems, which may limit the extrapolation of our findings to low-resource settings, such as parts of Brazil. While IV access is universally available and inexpensive, IO access requires specific devices and training, which may represent an additional challenge in these contexts. Future studies should evaluate not only clinical outcomes but also economic and logistical aspects to inform decision-making across diverse healthcare systems better.

This systematic review and meta-analysis demonstrated that IO access is comparable to IV access for clinical outcomes in patients with OHCA. Both methods showed no significant differences in survival with favorable neurological outcomes, ROSC, sustained ROSC, or survival to hospital discharge. These findings highlight the equivalence of IO and IV access, emphasizing the flexibility of either method based on clinical circumstances, such as vascular access difficulty or available time. While IV access remains the standard in many protocols, IO access is an effective alternative, especially in challenging situations. The results of this study can guide clinical decision-making in emergency settings, ensuring that the choice of vascular access method aligns with the patient's needs and available resources. Further research, particularly with larger and more diverse samples, is needed to strengthen these findings and address potential limitations.