Resuscitative endovascular balloon occlusion of the aorta (REBOA) in patients with major trauma and uncontrolled haemorrhagic shock: a systematic review with meta-analysis

Haemorrhage from non-compressible torso injuries is a leading cause of death in military and civilian trauma [1]. To control exsanguinating bleeding from non-compressible torso injuries, a damage control approach should be used. A variety of damage control surgery techniques have been developed to limit blood loss, control contamination and preserve one’s physiology such as abdominal packing, non-essential organ removal, extra-peritoneal packing, stapler resection of the bowel, vascular shunts and interventional radiology with embolization procedures.

Resuscitative thoracotomy is commonly used in patients in extremis or cardiac arrest for open cardiac massage and aortic cross-clamping [2, 3]. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a technique for temporary cessation or limitation of blood flow through the aorta, which may be used as a bridge until definitive control of the bleeding by endovascular procedures or surgery is performed [4]. After emergency room extended focused assessment sonography for trauma (E-FAST) and chest and pelvis x-ray, the balloon can be inflated in the descending thoracic aorta (zone 1) to reduce blood flow below the diaphragm or in the abdominal aorta below the renal arteries (zone 3) to stop bleeding from the pelvis and lower extremities.

The application of a REBOA has been suggested in the following cases: (i) in zone 1 for imminent traumatic cardiac arrest for probable haemorrhagic cause [5]; (ii) in zone 1 for severe haemorrhagic shock due to abdominal and/or pelvic injuries [6, 7]; (iii) in zone 3 for severe pelvic fracture [7, 8] or to control junctional bleeding from the groin end lower extremities; (iv) in zone 1 for penetrating thoracic trauma, according to an algorithm proposed in 2020 [9].

In recent years, REBOA has received a lot of attention for its applicability and promise in adult major trauma settings. It is a less invasive method of haemodynamic control in severe haemorrhagic settings relative to other damage control techniques. Survival benefits between REBOA and non-REBOA in severe abdominal-pelvic haemorrhage and between REBOA and resuscitative thoracotomy (RT) in imminent cardiac arrest for haemorrhage are controversial. All procedures may lead to unintended adverse effects [10] and this underlines the need for shared indications for the use.

The aim of this systematic review was to explore to the best of current knowledge if REBOA is clinically safe and effective in the management of major exsanguination from torso injuries due to trauma.

We conducted a systematic review to support the major trauma integrated management guideline panel of the Italian National Institute of Health (Istituto Superiore di Sanità) in formulating recommendations [11]. Following the GRADE-ADOPOLMENT methodology [12] and in accordance with the standards defined by the Sistema Nazionale Linee Guida (SNLG) [13], the multidisciplinary panel decided to develop a “de novo” question addressing the efficacy of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) on patients with major trauma. The clinical question addressed in this systematic review was: Is Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) clinically effective in the Management of major exsanguination in trauma?

To our knowledge, this is the first comprehensive systematic review and meta-analysis assessing all comparisons between REBOA and RT and REBOA versus no-REBOA, considering many critical and important outcomes. With low quality of evidence, adjusted overall estimates found a difference in favour of REBOA when compared to RT (aOR 0.38; 95% CI 0.20–0.74). With very low quality of evidence, REBOA when compared to no-REBOA (aOR 1.40; 95% CI 0.79–2.46) did not show a significant difference in outcomes. Adverse events were poorly reported across studies: only four studies reported complications such as amputation, haematoma and pseudoaneurysm.

Our literature search found five systematic reviews about the use of REBOA. However, two investigated the REBOA in a variety of clinical settings [10, 32], and one focussed only on adverse events revising case series studies [33]. Our results are consistent with other two systematic reviews [34, 35] where the comparison of REBOA versus RT found similar quantitative findings (aOR 0.42; 95%CI 0.17–1.03; OR 0.25; 95%CI 0.11–0.56, respectively). Nevertheless, our review updated the evidence including the last three years of publication.

All the studies where REBOA was compared to RT [21‐24, 29] demonstrated a clear survival benefit in very sick patients. This statistical significance can be biased since the most serious patients in cardiac arrest or imminent cardiac arrest undergo a RT, while more stable patients might be considered for REBOA. In very sick patients with very low critical tissue and organ perfusion or impending cardiac arrest, extreme resuscitative manoeuvres are required as a bridge to save time to definitive bleeding control or other potential reversible injury management. RT is a maximally invasive procedure in the trauma setting with a survival of less than 10% but associated with a negative perception because often used as the last resort in patients beyond saving [36, 37]. In this comparison, patient selection separates patients into the dead-or-nearly-dead (RT) and the alive-but-severe-shock (REBOA) with no valid conclusions regarding the superiority or preference of REBOA over RT. Therefore, in the absence of randomized trials, REBOA can only be considered an option for the clinician in very sick haemorrhagic patients following trauma. The more valuable contribution to the literature should come from the comparison of REBOA and no-REBOA. However, when REBOA has been compared with no-REBOA in our analyses [25‐27, 30] a clinical benefit was not observed. The available published studies range from very low and low certainty of evidence, including patients with brain injuries or chest injuries on which REBOA has no benefit and sometimes can be harmful. Moreover, the evidence was limited to observational studies. In all studies, the clinical indication to REBOA was haemorrhage from a pelvic fracture or abdominal injury, conditions that recognize optimal clinical results with standard damage control approaches, such as abdominal or extraperitoneal packing [38]. Both manoeuvres improve haemodynamics and survival and are easily performed by surgical personnel with specific experience.

REBOA stops flow totally or partially below the occlusion level (zone I or III), inflation limits the bleeding but also does produce ischemia both regionally and systemically. Given the tendency towards reperfusion injury, REBOA has a limited time window of application before the complications overcome the benefit of intervention [39, 40]. REBOA is likely not clinically better than the standard and more consolidated damage control interventions for bleeding control in non-compressible torso haemorrhagic shock, but can be implemented as a life-saving haemostatic bridge, if damage control surgery is not immediately available after prompt evaluation and indications based on clinical characteristics of patients. Furthermore, many variables can affect survival in this category of patients: pre-hospital time, prompt recognition of bleeding site(s), availability of expert surgeon, time to operating room, appropriate transfusion protocol, physiology of the patient. Time to operating room and physiologic state of patients may predict outcome as importantly as does whether a REBOA is used [41]. Due to these considerations, further investigations with an adequate volume of cases considering all possible confounders can help to understand the efficacy of REBOA in torso haemorrhages.

Our review is the most comprehensive effort in the management of haemorrhage in major trauma patients; however, several limitations must be addressed. Although our quantitative synthesis shows that REBOA is associated with lower mortality when compared to RT, these results could be flawed by the presence of patient selection for indication bias and survival bias within the individual observational studies [42]. Indication bias arises when patients are classified on the basis of the non-randomized intervention they received during the natural course of their medical treatment. Survival bias appears when comparing groups in which patients may die before treatment is initiated [43]. Clinical conditions (e.g. cardiac arrest) strongly influenced the treatment indication and so the assignment of patients in the RT or no-REBOA group. In the emergency department, RT is performed in patients who are experiencing post-traumatic cardiac arrest, while REBOA is indicated for trauma patients who are in an uncontrolled haemorrhagic shock for a pelvic fracture or abdominal fluid detected on an initial ultrasonography scan in the trauma bay [27]. For these reasons, some studies may have an inadequate control group (i.e. patients who did not undergo REBOA placement and/or RT). We have overcome this limitation by subgrouping the patients, who underwent thoracotomy in the ED, patients who underwent REBOA and those who did not undergo REBOA. Unfortunately, we did not find RCTs, the most reliable evidence on the effectiveness of interventions [44] which minimize the risk of bias and confounding factors influencing the results [45]. Even if performing RCTs can be unethical in life-threatening situations, challenging to design and deliver it is not impossible: a recent mapping review has highlighted that evidence from trials in prehospital trauma is sparse and can be prioritized [46]. We call for the need for further randomized trials of REBOA vs RT and REBOA vs no-REBOA in order to assure well-matched patients.

The use of REBOA should take into account skills, high expertise on their applicability [47, 48], acceptability of clinicians and cost [49, 50]. For optimal success, REBOA requires careful system-wide multidisciplinary implementation [51]. Institutions are responsible for analysing qualifications for providers to perform REBOA [42] as well as evaluating system capabilities [52]. A very small number of trauma centres have an extensive experience with REBOA; thus, these results may not be generalizable to all trauma centres [42]. Finally, we included studies with a heterogeneous use of REBOA which should be taken into account (catheter size, occlusion zone, protocols, physiologic indications for REBOA insertion).

Among non-compressible torso injuries, we found a positive effect on overall mortality of REBOA when compared to RT but no valid conclusions can be made due to selection bias, while not statistically significant the comparison of REBOA versus no-REBOA from which the most valuable contribution for clinical practice is drawn. REBOA should be promoted in specific training programs in an experimental setting in order to test its effectiveness as temporary management to haemorrhage control and resuscitation. Prospectively assessed data, with specific inclusion and exclusion criteria, ideally in a randomized controlled trial, should be planned in order to limit the bias coming from observational studies. Future studies must address specific indications for REBOA to know which population could benefit the most from its use.