The UK-REBOA trial

REBOA (resuscitative endovascular balloon occlusion of the aorta) has been discussed in the emergency medicine world for quite some time now, but always with very limited data. There have been some observational studies that suggested REBOA was associated with worse outcomes, but the outcomes were largely assumed to be the result of confounders. (Norii 2015, Joseph 2019) There was also some more positive observational data. (Manzano Nunez  2017; Borger van der Burg 2018) This year, we saw the first RCT published, in the form of the UK-REBOA trial.

The paper

Jansen JO, Hudson J, Cochran C, et al. Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial. JAMA. 2023 Nov 21;330(19):1862-1871. doi: 10.1001/jama.2023.20850. PMID: 37824132

The Methods

The UK-REBOA trial is a multicenter open label RCT from 16 trauma centers in the United Kingdom.

Patients

Trauma patients 16 years or older with confirmed or suspected life threatening torso hemorrhage which was deemed amenable treatment with REBOA. Exclusions: Pregnancy; injuries that were clearly unsurvivable. 

Intervention

REBOA plus standard care.

Comparison

Standard care alone. 

Outcome

The primary outcome was all cause mortality at 90 days.

The Results

They enrolled 90 patients, 89 of whom have data for the full 90 days. The trial was stopped early because a planned stopping point for harm was met.

These were sick trauma patients (with a median injury severity score of 41). As expected, they were mostly young males. The vast majority (97%) was blunt trauma. There is some evidence of baseline imbalance between the groups, with hypotension at enrollment being more common in the REBOA group. However, somewhat strangely, heart rates were significantly higher in the standard care group. (I would have suspected hypotension and tachycardia to go together). 

Only 41% of the REBOA group actually had a REBOA device inflated. 37% improved while the procedure was being performed, and the other 21% either died before arterial access was possible, or the procedure was attempted but failed.

Of the patients who had the REBOA device inflated, about half had it in zone 1 (the descending thoracic aorta) and the other half in zone 3 (above the aortic bifurcation). Median time from arrival to inflation was 32 minutes, and median time of inflation was 29 minutes.

Mortality was higher in the REBOA group (54% vs 42%, OR1.58, 95%CrI 0.72-3.52). Based on their Bayesian analysis, they conclude a 87% chance that REBOA increases mortality and only a 4% chance that it decreases mortality.

My thoughts

Although I have been talking about REBOA from very early on (I remember asking a trauma team leader about this years ago, and they had no idea what I was talking about), I have never seen a REBOA device in use, and I have never even seen one in a simulation setting. That limits my ability to comment on the clinical intricacies of the procedure, and when you are assessing procedures, those clinical details often matter a lot. (Consider the research looking at the use of bougie for intubation, as an example.) 

The fact that less than half of the REBOA group actually had a REBOA device inflated obviously biases against the device (if it works), but is perhaps representative of real world numbers. (This is the difference between efficacy and effectiveness trials. A device that works perfectly if placed, but which cannot be placed most of the time, is not going to be a helpful device.)

The numbers in this trial seem to suggest that the clinicians were relatively inexperienced with REBOA. They failed to cannulate the artery 17% of the time and took more than 30 minutes to complete the procedure, which seem like high numbers to me (but again, I have no personal experience with this device).

This trial does not include a standard sample size calculation, because they designed the trial around Bayesian statistics. At some point, we are going to have to do a deeper dive into the Bayesian statistics we are starting to see in trials. In fact, I think Dr. Anand Senthi might contribute a guest post on the topic at some point. The short version is that this method of statistical analysis provides a huge amount of freedom to researchers, allows for overly optimistic priors to be selected, and seems to use some math that is usually overly optimistic. (I am still trying to wrap my head around the math, so I really hope Anand finds the time to educate us all.)

These results will not apply to all trauma systems. These patients did not arrive at the hospital until 90 minutes after their injury, likely representative of the UK physician led prehospital trauma teams, which are more likely to ‘stay and play’ on scene than paramedic led teams in North America. As REBOA was only performed in hospital in this study, this might represent a very significant delay which could bias the results against REBOA. (Generalizability is also affected by the fact that these were essentially all blunt trauma patients, so we can’t really say anything about penetrating trauma.)

The delay to hospital arrival also makes selection bias a bigger issue, when thinking about these results from a North American perspective. Patients that were still alive after 90 minutes of resuscitation might have better outcomes than those who crash through the door rapidly, and so we might see more REBOA activations in North America. Selection bias is compounded by the subjective criteria that patients had to be ‘amenable to REBOA’ according to the treating physician, which is reasonable but does introduce the possibility of biased patient selection. Additionally, I wonder about the use of ‘clearly unsurvivable’ as an exclusion. It makes sense, but I would like to know how good physicians are at this determination. Did all of these patients actually die?

Finally, outside of mortality, I don’t see other harms from REBOA mentioned. Were there ischemic limbs or ischemic bowel that could make these results even worse?

Bottom line

UK-REBOA is the first RCT of REBOA, and demonstrated an increase in mortality. That is not what we were hoping for, and should temper enthusiasm for this procedure. Of course, this is nowhere close to a perfect trial, and we definitely need to see a lot more research in this area to be sure. However, I don’t think that REBOA makes sense outside of a research setting after these results. 

Other FOAMed

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

The Bottom line: Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage

REBEL EM: UK-REBOA on Trial: Innovative or Over-Inflated?

Evidence based medicine is easy

The EBM bibliography

Evidence based medicine resources

EBM deep dives

References

Borger van der Burg BLS, van Dongen TTCF, Morrison JJ, Hedeman Joosten PPA, DuBose JJ, Hörer TM, Hoencamp R. A systematic review and meta-analysis of the use of resuscitative endovascular balloon occlusion of the aorta in the management of major exsanguination. Eur J Trauma Emerg Surg. 2018 Aug;44(4):535-550. doi: 10.1007/s00068-018-0959-y. Epub 2018 May 21. PMID: 29785654

Jansen JO, Hudson J, Cochran C, MacLennan G, Lendrum R, Sadek S, Gillies K, Cotton S, Kennedy C, Boyers D, Ferry G, Lawrie L, Nath M, Wileman S, Forrest M, Brohi K, Harris T, Lecky F, Moran C, Morrison JJ, Norrie J, Paterson A, Tai N, Welch N, Campbell MK; UK-REBOA Study Group; Aylwin C, Bew D, Brooks A, Chinery J, Cowlam T, Frith D, George A, Hudson A, Johnstone P, Mahmood A, Novak A, O’Meara M, Reid S, Sattout A, Smith C, Stansfield T, Thompson J. Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial. JAMA. 2023 Nov 21;330(19):1862-1871. doi: 10.1001/jama.2023.20850. PMID: 37824132

Joseph B, Zeeshan M, Sakran JV, Hamidi M, Kulvatunyou N, Khan M, O’Keeffe T, Rhee P. Nationwide Analysis of Resuscitative Endovascular Balloon Occlusion of the Aorta in Civilian Trauma. JAMA Surg. 2019 Jun 1;154(6):500-508. doi: 10.1001/jamasurg.2019.0096. PMID: 30892574

Manzano Nunez R, Naranjo MP, Foianini E, Ferrada P, Rincon E, García-Perdomo HA, Burbano P, Herrera JP, García AF, Ordoñez CA. A meta-analysis of resuscitative endovascular balloon occlusion of the aorta (REBOA) or open aortic cross-clamping by resuscitative thoracotomy in non-compressible torso hemorrhage patients. World J Emerg Surg. 2017 Jul 14;12:30. doi: 10.1186/s13017-017-0142-5. PMID: 28725258

Norii 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 Apr;78(4):721-8. doi: 10.1097/TA.0000000000000578. PMID: 25742248

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