REBOA and the Challenge of Research in Critical Illness September 2023 Annals of Emergency Medicine Journal Club

Cralley AL, Vigneshwar N, Moore EE, et al. Zone 1 endovascular balloon occlusion of the aorta vs resuscitative thoracotomy for patient resuscitation after severe hemorrhagic shock. JAMA Surg. 2023;158(2):140-50. In the management of patients with severe traumatic hemorrhagic shock, is zone 1 endovascular balloon occlusion of the aorta (REBOA) a safe and effective option compared to resuscitative thoracotomy (RT)? Design: Multicenter, observational, prospective cohort. Setting: Twenty-eight US trauma centers participating in the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry from 2013 to 2021. Population: Trauma patients 16 years and older undergoing aortic occlusion (AO) during resuscitation in the emergency department (ED). Intervention: AO with zone 1 REBOA or RT. Primary Outcome: Inhospital survival. Secondary Outcomes: Ventilation-free days, intensive care unit free days, Glasgow Coma Scale Score, and Glasgow Outcome Score on discharge. Sponsors: The study was supported in part by grants from the National Institute of General Medical Sciences of the National Institutes of Health and from the Department of Defense. Out of 900 patients in the registry, the population included for analysis was comprised of 56 patients in each group. After using propensity score matching and adjusting for confounders, the authors found RT was associated with significantly higher mortality than REBOA zone 1 (adjusted relative risk, 1.25; 95% confidence interval, 1.15-1.36). Additionally, REBOA zone 1 offered similar or superior survival in all analyzed subgroups. There were no significant differences between REBOA and RT in any of the prespecified secondary outcomes. The results of this study suggest REBOA is an effective alternative to RT when resuscitating ED patients in severe hemorrhagic shock requiring AO. The implications of these findings may prompt ED providers to consider REBOA as a first-line intervention when managing patients with severe hemorrhagic shock. However, the results from an observational study, even with propensity score matching, should be interpreted with caution. Although propensity score matching attempts to mitigate selection bias, it cannot eliminate the effect of this bias on outcomes. Additionally, when there are large differences between groups, as seen in this study with illness severity, no amount of propensity score matching is adequate. Although full publication is not yet available, the REBOA-UK results have recently been shared. This randomized controlled trial showed increased all-cause mortality in the REBOA group at 90 days and increased death from hemorrhage at 3 hours and 90 days. The conflicting results of REBOA-UK to the prior observational data underscore the importance of waiting for high-quality data prior to instituting practice change. Q1: What is REBOA? What are the clinical indications for this procedure? REBOA is the percutaneous placement of an intra-arterial balloon into the descending aorta to achieve AO. It serves as a minimally invasive alternative to open aortic cross-clamping in the management of patients with severe, noncompressible hemorrhage arising below the diaphragm. REBOA limits arterial flow below the level of the balloon whereas also improving central perfusion pressure by increasing afterload proximal to the balloon.1Cantle P.M. REBOA utility.Surg Open Sci. 2022; 8: 50-56Crossref PubMed Scopus (2) Google Scholar This provides the resuscitation team a short window of time to (A) rapidly increase the volume of a smaller, fluid circuit; (B) attempt to achieve a return of spontaneous circulation in the setting of a traumatic cardiac arrest by increasing coronary blood flow; and (C) identify the hemorrhage source and determine the ideal location and strategy for its definitive management.1Cantle P.M. REBOA utility.Surg Open Sci. 2022; 8: 50-56Crossref PubMed Scopus (2) Google Scholar REBOA is used to temporize patients at high risk of mortality from noncompressible torso hemorrhage, as it is not a definitive hemorrhage control device.2Zakaluzny S.A. Beldowicz B.C. Salcedo E.S. et al.Guidelines for a system-wide multidisciplinary approach to institutional resuscitative endovascular balloon occlusion of the aorta implementation.J Trauma Acute Care Surg. 2019; 86: 337-343Crossref PubMed Scopus (19) Google Scholar Several studies report successful 30-day survival following brief periods of AO (20-40 minutes); however, longer periods of AO are associated with increased mortality.3Saito N. Matsumoto H. Yagi T. et al.Evaluation of the safety and feasibility of resuscitative endovascular balloon occlusion of the aorta.J Trauma Acute Care Surg. 2015; 78: 897-903Crossref PubMed Scopus (182) Google Scholar, 4Norii T. Crandall C. Terasaka Y. Survival of severe blunt trauma patients treated with resuscitative endovascular balloon occlusion of the aorta compared with propensity score-adjusted untreated patients.J Trauma Acute Care Surg. 2015; 78: 721-728Crossref PubMed Scopus (157) Google Scholar, 5Stannard A. Eliason J.L. Rasmussen T.E. Resuscitative endovascular balloon occlusion of the aorta (REBOA) as an adjunct for hemorrhagic shock.J Trauma Acute Care Surg. 2011; 71: 1869-1872Crossref Scopus (389) Google Scholar, 6Holcomb J.B. Fox E.E. Scalea T.M. et al.Current opinion on catheter-based hemorrhage control in trauma patients.J Trauma Acute Care Surg. 2014; 76: 888-893Crossref PubMed Scopus (44) Google Scholar Achieving the appropriate positioning of REBOA is paramount, and for this reason, the aorta is divided into 3 separate anatomic zones:•Zone I of the aorta extends from the origin of the left subclavian artery to the celiac artery.•Zone II extends from the celiac artery to the most caudal renal artery. This is considered to be a “no-occlusion” zone.•Zone III extends distally from the most caudal renal artery to the aortic bifurcation. Zone 1 REBOA can decrease bleeding from visceral injuries, including those to the liver, spleen, kidneys, and retroperitoneum. Zone 3 REBOA limits hemorrhage from both pelvic fractures and vascular injuries of the iliac arteries, lower extremities, and the junctional region of the groin. REBOA has also been used in zone 3 for cases of severe obstetrical bleeding, including placenta accreta spectrum.7Whittington J.R. Pagan M.E. Nevil B.D. et al.Risk of vascular complications in prophylactic compared to emergent resuscitative endovascular balloon occlusion of the aorta (REBOA) in the management of placenta accreta spectrum.J Matern Fetal Neonatal Med. 2022; 35: 3049-3052Crossref PubMed Scopus (21) Google Scholar,8Kluck S.L. Russo R.M. Appel N.B. et al.Aortic balloon occlusion in distal zone 3 reduces blood loss from obstetric hemorrhage in placenta accreta spectrum.J Trauma Acute Care Surg. 2023; 94: 710-717Crossref PubMed Scopus (4) Google Scholar Q2: It is challenging to obtain informed consent on patients with critical illness, making high-quality research challenging. What systems exist to address this issue? Informed consent is a central principle in human research as it provides essential protection to participants. It requires documentation of the discussion of the procedure; its risks, benefits, and reasonable alternatives; and an assessment the patient understands this discussion.9Bazzano L.A. Durant J. Brantley P.R. A modern history of informed consent and the role of key information.Ochsner J. 2021; 21: 81-85Crossref PubMed Scopus (26) Google Scholar It can be challenging to obtain informed consent when doing research on critically ill patients as capacity involves “the ability to understand relevant information, appreciate the present situation and its consequences, and the ability to manipulate information rationally.”10Appelbaum P.S. Grisso T. Assessing patients’ capacities to consent to treatment.N Engl J Med. 1988; 319: 1635-1638Crossref PubMed Google Scholar Altered mental status, delirium, and need for sedation compromise a patient’s capacity.11Verceles A.C. Bhatti W. The ethical concerns of seeking consent from critically ill, mechanically ventilated patients for research–a matter of possessing capacity or surrogate insight.Clin Ethics. 2018; 13: 107-111Crossref PubMed Scopus (5) Google Scholar The expediency with which treatment or intervention needs to be provided offers another barrier. Further, there is potentially perceived coercion; critically ill patients are a vulnerable patient group, and the consent discussion may imply receipt of the best medical care is predicated on an agreement to enroll in the study.12Ecarnot F. Quenot J.P. Besch G. Piton G. Ethical challenges involved in obtaining consent for research from patients hospitalized in the intensive care unit.Ann Transl Med. 2017; 5: S41Crossref PubMed Scopus (25) Google Scholar Overcoming these barriers to improve the quality of resuscitation research may involve several means to address these challenges. The use of surrogate decision makers, a designated proxy or family member, is an accepted alternative strategy but has numerous limitations: inability to identify a surrogate and emotional and psychological stress on the surrogate, which may influence decision making.12Ecarnot F. Quenot J.P. Besch G. Piton G. Ethical challenges involved in obtaining consent for research from patients hospitalized in the intensive care unit.Ann Transl Med. 2017; 5: S41Crossref PubMed Scopus (25) Google Scholar,13Burns K.E. Zubrinich C. Marshall J. Cook D. The ‘Consent to Research’ paradigm in critical care: challenges and potential solutions.Intens Care Med. 2009; 35: 1655-1658Crossref PubMed Scopus (29) Google Scholar Deferred consent is an approach where the patient is enrolled with the intention of obtaining consent when the patient regains capacity or when a surrogate can be identified. The recent REBOA-UK randomized control trial used differed consent in its process. This approach, however, raises ethical issues relating to randomization without consent and does not address how to handle data on patients who die and cannot give deferred consent.13Burns K.E. Zubrinich C. Marshall J. Cook D. The ‘Consent to Research’ paradigm in critical care: challenges and potential solutions.Intens Care Med. 2009; 35: 1655-1658Crossref PubMed Scopus (29) Google Scholar Waiver of consent likely provides the best potential solution. The Food and Drug Administration allows internal review boards to approve research without informed consent if certain conditions are met: the patient has a life-threatening situation, obtaining consent is not feasible, and the intervention provides a chance for direct benefit12Ecarnot F. Quenot J.P. Besch G. Piton G. Ethical challenges involved in obtaining consent for research from patients hospitalized in the intensive care unit.Ann Transl Med. 2017; 5: S41Crossref PubMed Scopus (25) Google Scholar (Food and Drug Administration Regulation 21 Code of Federal Regulations 50 and 56). Waiver of consent has provided a means to enhance enrollment for studies involving the critically ill and would apply to an intervention such as REBOA.14Annane D. Outin H. Fisch C. Bellissant E. The effect of waiving consent on enrollment in a sepsis trial.Intens Care Med. 2004; 30: 321-324Crossref PubMed Scopus (64) Google Scholar