JC: The UK-REBOA trial. Has the balloon popped? St Emlyn's • St Emlyn's

Since its emergence over a decade ago as a potential tool to manage the patient with non-compressible torso hemorrhage, resuscitative endovascular balloon occlusion of the aorta (REBOA) has been the marmite of the trauma world – people either love it or hate it. Needless to say, the social media reaction following the release of the UK-REBOA trial at the Critical Care Reviews meeting in Belfast earlier this month was predictable. The trial’s negative results (the first randomized-controlled trial [RCT] for this procedure) seemed to be an early Christmas present for those in the anti-REBOA camp.

Many know I am in favor of any tool that could potentially reduce the potentially preventable death rate we continue to see despite decades of trauma innovation. REBOA is one such tool. It is however imperative to listen to the science – and also to evaluate it critically. The full paper is not out as yet, and so this review is based on the data presented at the #CCR23 conference. That means you should be especially sceptical of our opinion below, as we hope you always are. We may learn more when the full paper is published and these should be considered early thought.

What did they do?

The authors conducted a RCT comparing the addition of REBOA to standard care (SC) of major trauma patients presenting to 16 major trauma centers in England. Bayesian methodology was used. 120 patients were planned to be enrolled with a primary outcome of 90-day mortality.

What were the headline results?

90 patients (46 in SC + REBOA arm) were enrolled from 2017 to 2022, with the trial being stopped early after a pre-defined stopping rule for harm was met. These patients had a median injury severity score (ISS) of 41. Median systolic blood pressure (SBP) in the REBOA arm was 84mmHg vs 99mmHg in SC arm. 19 patients in the REBOA arm actually got the procedure as did 2 in the SC arm. At 90 days, 54% of the REBOA patients were dead vs 42% in the SC arm (OR 1.58).

UK-REBOA results:

REBOA increased mortality at 90 days and at all interim time points.

REBOA increased deaths due to bleeding at 3 hours and 90 days.

REBOA substantially delayed time to definitive haemorrhage control.

💢🎈💢#ccr23 pic.twitter.com/yGPoDTJC0Z
— Karim Brohi (@karimbrohi) June 14, 2023

Don’t just read the Twitter abstract!

There were several knee-jerk reactions after Prof. Karim Brohi posted on Twitter, which I found akin to just “reading the abstract” and forgoing the details. Whether or not this is a nail in the coffin for REBOA is yet to be decided, and some key context must be taken into account. Remember, the full paper has yet to be published.

Are the patients in each group the same?

An RCT should ensure that the control and intervention arms are well-matched. The trial authors advised the trauma team leader to use a telephone app to randomize eligible patients. Each arm had an equal ISS (46) implying critical injury. Each group also had similar Abbreviated Injury Scores (AIS) for all body region, except the head. The REBOA arm had a median head AIS of 3 (defined as a serious head injury) versus a head AIS of 0 in the control arm. This is important – concomitant significant traumatic brain injury (TBI) can affect both mortality and functional outcome. In fact, 2 patients died within 3 hours in the REBOA group from TBI – none did in this time period in the SC group.

Were the patients in the REBOA arm sicker? Although the ISS was equal, a greater proportion of patients in the REBOA arm had systolic blood pressures (SBP) ≤70mmHg in the pre- and in-hospital settings. Davis et al in their review of 1174 trauma patients requiring a laparotomy reported a significantly higher mortality in the group with SBP ≤70mmHg. Perhaps these patients would not have survived despite all resuscitative efforts.

Why, in a randomized trial, were there these group differences? This segues to the number randomized. The aim was to have 120 patients but only 90 ended up being included. This is a relatively low number in general. Had they continued to 120 patients, perhaps the groups would have been better matched.

Time matters

There may be many controversies in trauma care, but the benefit of stopping the bleeding as soon as possible is not one of them. Chang et al, in reviewing the data from the PROPPR trial, showed that every 15-minute delay in hemostasis was associated with increased 30-day mortality, acute kidney injury, ARDS, and multiorgan failure.

Prehospital time in both arms was about 90 minutes from injury to ED arrival. This likely reflects UK prehospital care, where an advanced critical care team may manage the patient on scene. However, in this trial, if this team was used, they did not seem to add benefit in terms of achieving early temporary hemorrhage control. Perhaps this meant the writing was on the wall for the REBOA arm patients.

Only 14 of the 46 REBOA arm patients and 19 of the SC arm patients actually underwent a hemorrhage control procedure. Times varied significantly. For the SC arm, the mean time from randomization to procedure was 65 minutes versus 155 minutes in the REBOA arm. Add to that the prehospital time of about 90 minutes and the REBOA patients were likely continuing to bleed for just over 4 hours from injury. Even the SC group patients waited over 2 hours. To me, this implies that there is a systems-level breakdown. REBOA is only a bridge to definitive care. If they need an urgent hemorrhage control procedure, there needs to be an urgency to provide that procedure! We specified this in our joint statement on the use of REBOA:

Let’s talk a little more about experience and the procedure

19 of 46 patients in the REBOA arm got the procedure, of whom only 14 underwent a hemorrhage-control procedure. Two patients in the SC arm also received REBOA. This small percentage of patients reflects that there are injury patterns that are deemed to need temporary hemorrhage control techniques, and that REBOA remains a tool in the box for those patients. From a patient-centered perspective, this is good to show that this technique should not be applied widely, but from a research perspective, it leaves us with too few patients to draw a meaningful conclusion in either direction.

The procedure itself took a median of 32 minutes. Again, this is a period of time the patients are continuing to bleed (and already >90 minutes post-injury). Perhaps this is not surprising as individual (center and person) experience in this study is likely low. Although the study authors made a valiant effort at training and skill maintenance, and I am sure each individual clinician put in their best effort, the reality of doing the procedure on a live person who is actively dying is very different than the training that happens on currently-available simulators.

I have long said that the initial step, obtaining arterial access, is the most challenging and time-consuming part of the procedure. In expert hands (through not only experience with REBOA at high-volume centers but also changing practice, as we have, to more often placing femoral arterial lines in all our critically-injured patients) this time is often less than 5 minutes. The latter step allows skill maintenance, increased proficiency, more dynamic patient monitoring, and provides a ready means to proceed with REBOA in the small number of people who may go on to need it.

The procedure and equipment have also evolved from 2017, to include partial REBOA and newer devices. Our understanding of complications has allowed us to alter practice to mitigate them.

Is the end-point valid?

The study used 90-day mortality as its primary outcome. Although this is certainly an important study variable, it may not be most appropriate for a patient group who traditionally has died within the first 6 hours of sustaining a torso injury – the exact time period for which REBOA was designed to help. Professors Brohi and Holcomb published an interesting opinion piece highlighting the importance of both cardiogenic failure and persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) primarily contributing to deaths beyond 24 hours. Hence, it may be difficult to tease out what contribution REBOA had to the longer-term outcomes.

Wow. UK 🇬🇧 REBOA Trial: REBOA + std care ⬆️ 90 day (& earlier time points) all-cause mortality – ⬆️ risk of mortality due to haemorrhage… Why? Likely due to ⬇️ no. of pts undergoing haemorrhage-control procedures & ⬆️ in time 🕰️ to procedure #ccr23 #ukreboatrial @karimbrohi pic.twitter.com/DYcsYqHweS
— Dr Stephen T Webb (@stephen_t_webb) June 14, 2023

What should we take-away?

I applaud the authors for their hard work. This was not an easy trial to pull off, even without the pandemic occurring in the middle of it. The data is certainly useful, and informs us more fully on not only the procedure, but the system in which it is used. My main thoughts are:

Time to bleeding control is critical – too much time passed from injury to a definitive hemorrhage control procedure (or even temporary hemorrhage control with REBOA) to be of benefit to these patients
Systems of care are critical – the centers did not demonstrate an ability to rapidly initiate definitive hemorrhage control procedures. This is a major problem in the care pathway for these types of patients
Experience matters – this is true both for experience that comes from patient volume as well as from doing the procedure. Remember, it is not easy accessing the femoral artery in dying patients. This requires deliberate training and skill maintenance in real patients. While few patients may need a REBOA, the sickest will benefit from invasive monitoring. One of the ways of doing this is to obtain early femoral arterial access in all critically-ill or -injured patients. This allows you to achieve a marginal gain should you need to proceed to REBOA.
REBOA may be needed in critically bleeding trauma patients before they arrive to UK MTCs – given the norm in many parts of the UK of having advanced physician-staffed prehospital teams attend to many major traumas, they might be in the best position to provide this procedure to achieve temporary hemorrhage control. This must however be done within a system of expeditious delivery of the patient to definitive care, which may include bypassing the ED and going directly to theater.

Ultimately this study highlights what many expert REBOA users have said already – that it is not a panacea. It is a tool in the box that requires clear indications for use in a select group of patients within a system of care that can deliver expeditious definitive hemorrhage control. The trial emphasizes that when used outside of these parameters, there is a real potential of harm. Similar harm can result, of course, when the details of such trials are not closely scrutinized.

Stay safe.

Zaf