Authors’ response: balloon size and interpretation of the REBOARREST trial Authors: Jostein Rødseth Brede, Andreas Jørstad Krüger Published: 2026 Main text We would like to thank the authors of the Matters Arising comment [1] for their interest in our recently published REBOARREST trial [2], in which resuscitative endovascular balloon occlusion of the aorta (REBOA) was used as an adjunct to advanced life support in non-traumatic out-of-hospital cardiac arrest. The authors raise important points, some of which were addressed in our original manuscript. We welcome the opportunity to elaborate and clarify these issues further. First, the question regarding regulatory approval prior to trial onset can be answered directly. All relevant approvals required for trial conduct and use of respective REBOA equipment were obtained before trial initiation in the participating countries. This included approval from relevant ethics committees, institutional authorities and competent medical-device authorities. This regulatory framework and agreements were described in the trial protocol [3]. We agree that exclusion of randomized patients due to missing deferred consent is a limitation that may distort the sample and should be considered when interpreting the results. In cardiac arrest research, inability to obtain deferred consent may be associated with early death and can introduce attrition bias. However, this was not a post hoc methodological decision, but a requirement by the ethical committees. As researchers, we were required to comply with these regulations. The authors cite an aortic diameter in the descending thoracic aorta of approximately 30 mm for 70 year-old individuals [4]. This is a relevant reference, but it represents one population-based estimate and may not be universally applicable. Mansouri et al. [5] reported a mean descending aortic diameter of approximately 24 mm based on data from eight studies [6–13], while the Framingham Heart study reported 25,8 mm (men) and 23,1 mm (women) from 3431 participants [14]. Smaller diameters have been reported for African and Asian populations [15, 16]. Aortic dimensions may vary with age, sex and body size. Thus, even if a 20 mm balloon may not provide complete geometrical occlusion in all patients, a single population-based estimate of aortic diameter should not be used to conclude that the balloon was insufficient in the individual patients enrolled in the trial. In REBOARREST, all study sites in Norway and Denmark used the 20 mm balloon from Reboa Medical, while the Italian site used ER-REBOA from Prytime, in accordance with the relevant national requirements. Patient safety was an overarching consideration during the entire trial, also when selecting equipment. It was considered important that the equipment used in the prehospital setting was familiar to the receiving in-hospital teams. Hence, equipment that was already in use at the participating hospitals, and had been used in the preceding pilot studies [17, 18], was selected. The potential for the balloon to be smaller than the aorta in some patients, and the theoretical reduction in risk of harm to the aortic wall, was among the safety considerations discussed with relevant authorities. We agree that it is likely true that effective aortic balloon occlusion requires adequate occlusion of the aortic lumen. We also agree that complete aortic occlusion cannot be assumed in every patient treated with a 20 mm balloon, especially in patients with larger aortic diameter. However, what is adequate occlusion? A residual aortic lumen does not by itself mean that the intervention was physiologically ineffective. The relationship between residual lumen and blood flow during resuscitation is likely complex, where factors such as the generated pressure gradient, vessel compliance, balloon position and blood viscosity may play a role. REBOARREST did not include direct measurements of intra-aortic pressure or flow, and we cannot determine the degree of aortic occlusion achieved in individual patients. We do not believe that the aorta acts as an immovable tube during chest compression and that incomplete geometrical occlusion should automatically equate to no hemodynamic effect. Decades ago, preclinical studies reported a reduction in aortic diameter during chest compressions [19]. More recently, Hwang [20] demonstrated deformation of the descending aorta during compressions in patients. This illustrates that static measurements obtained outside cardiac arrest cannot necessarily be assumed to represent the effective aortic lumen during chest compressions. However, these observations do not allow us to conclude that a 20 mm balloon would achieve complete occlusion in individual patients, and it is therefore appropriate to say that REBOARREST cannot establish the efficacy of complete aortic occlusion with the balloon size used. However, the significant increase in end-tidal carbon dioxide after aortic occlusion is compatible with a physiological effect of the intervention, although it cannot establish the degree of aortic occlusion or clinical benefit. We therefore agree that treatment fidelity with respect to adequate occlusion is a limitation and should be an important consideration for future trials. The timing of treatment delivery is one of the main limitations of REBOARREST. At the same time, we consider this to be one of the most important findings. It is important to bear in mind that REBOARREST was deliberately designed as a pragmatic trial, to evaluate the intervention in routine prehospital care, rather than in a laboratory or in a proof-of-concept observational trial. In our mixed urban-rural North European setting, with REBOA deployment performed by physician-led teams, balloon occlusion occurred at a median of 47 min after cardiac arrest. Aortic occlusion during cardiac arrest is likely a time-dependent physiological intervention. Thus, the trial cannot distinguish between lack of biological efficacy of aortic occlusion and lack of efficacy when aortic occlusion is initiated this late during cardiac arrest. This is an important distinction. REBOARREST tested whether a strategy of prehospital deployment of REBOA as an adjunct to advanced life support, implemented in a real-world emergency medical service, increased the rate of sustained return of spontaneous circulation. It did not. Whether a different REBOA strategy – earlier, faster and with reliable adequate aortic occlusion – can improve outcome, remains a hypothesis for future trials. That question remains unanswered by REBOARREST and should be addressed by a different trial, rather than being inferred from the limitations of this one. Acknowledgements Not applicable. Author contributions JRB drafted the article. AJK reviewed the article. Both authors approved the final version. Funding No funding was received for this work. Data availability No datasets were generated or analysed during the current study. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Footnotes Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References Associated Data Data Availability Statement No datasets were generated or analysed during the current study.