A look at the numbers:
- 19/90 patients had REBOA in the UK-REBOA Trial
- 16 Trial Sites
- 25 authors
As you read through my proposed additions to the published discussion of the UK-REBOA Trial JAMA article based on actual data from the paper, ask yourself this simple question: Is this really the definitive evidence that we have been seeking for or against REBOA in non-compressible torso hemorrhage in trauma?
What was said:
“Among the 90 patients who were enrolled in the current trial, the REBOA and standard care group was observed to have a high probability (86.9%) of higher mortality at 90 days (the primary outcome) compared with the standard care alone group. It is also noteworthy that the ORs and posterior probabilities for increased mortality increased with earlier time points, which are more specific for deaths due to hemorrhage. The findings were not altered in an adjusted analysis conducted to account for the baseline imbalances. The probability was 3.7% that REBOA and standard care reduces mortality by a worthwhile margin at 90 days, and less so at time points within 24 hours.”
What should have been added:
In this intention to treat RCT, there was significant crossover from the REBOA and standard of care group to the standard of care control group. Acknowledging that this wasn’t the UK-Femoral Access Trial, 17 patients (37%) in the REBOA and standard of care group received an arterial line (or not at all in 3 of these patients) but had no REBOA treatment “because [patients] responded to other resuscitative measures while REBOA insertion was being prepared or performed, and progression to full aortic occlusion was no longer deemed necessary”. Crossover can have important consequences on trial validity with high crossover potentially invalidating trial results. At the very least we should have done a sensitivity analysis to see if the crossover had any impact on the primary outcome. Regardless, considering the extremely low number of patients enrolled in our trial, we could not afford to censor or exclude any patients from crossover because we likely would not have obtained any statistical significance. Therefore, to be academically honest, we plan to publish a per-protocol/as-treated analysis of the mortality rates in patients that received the REBOA intervention.
What was said:
“The survival curves demonstrate the probable harmful early effects of REBOA (Figure 2B). The early (within the first few hours) decline in survival likely represents a delay or failure to definitively control hemorrhage as a result of REBOA insertion or during attempts at REBOA insertion in the emergency department.”
What should have been added:
However, as authors, we must acknowledge that 1 in 3 patients didn’t even get the balloon inflated because “progression to full aortic occlusion was no longer deemed necessary” due to an improved response from other resuscitative measures. Therefore, to state that REBOA was harmful early on due to a delay/failure to get definitive control of hemorrhage would be a tad misleading. We admit that it is hard for patients to both bleed to death and have improved hemodynamics at the same time.
What was said:
“There were fewer patients who underwent a definitive hemorrhage control procedure in the REBOA and standard care group, likely due to the competing risk of early death.”
What should have been added:
The major finding that we glossed over is the OR of 0.6 for a definitive hemorrhage control procedure in the REBOA and standard care group. In other words, there was a much higher chance of getting a hemorrhage control procedure in the non-REBOA group than the REBOA group. Knowing that 1 in 3 patients had apparently improved hemodynamically in the REBOA group, not necessitating balloon inflation, it is hard to explain why many of these same patients suddenly died and couldn’t get to the operating room for a definitive hemorrhage control procedure. Perhaps, many of the patients who died in the REBOA group without an inflated balloon should have actually had the balloon inflated to help them get to the operating room (AKA BRIDGE to a definitive hemorrhage control procedure.)
What was said:
“For those patients who did undergo such a [hemorrhage control] procedure, it took, on average, an additional 19 minutes to commence these procedures.”
What should have been added:
The Joint Statement ACS/COT ACEP best practice recommendations for REBOA clearly state that REBOA in Zone 1 should only be performed if the anticipated time to start of operation is less than 15 min. Therefore, since it took more than 60 minutes in both groups to even commence a hemorrhage control procedure, then very few patients should ever have even been enrolled in this trial in the first place. Also, if the sickest trauma patients (ISS 41!) can’t get to the OR in under 60 minutes at these hospitals, then this probably should have been highlighted as a potential confounder.
What was said:
“There were a number of treatment pathways experienced by patients in the REBOA and standard care group due to intercurrent events. These findings reflect the challenges in obtaining arterial access in patients with severe shock and in distinguishing between patients who are experiencing continuing hemorrhage from those in whom bleeding has stopped. These experiences reflect real life and highlight the complexity of trauma care, and the challenges inherent in evaluating it.”
What should have been added:
We acknowledge that we should have had an experienced group of physicians that had done a minimum amount of REBOA procedures before being allowed to recruit for this trial. Having a minimum procedural volume threshold to enter the study would likely have reduced the degree of crossover. Becoming competent in a study procedure is standard for other RCT’s but wasn’t truly accounted for in our study. For instance, in the early laparoscopic cholecystectomy versus open cholecystectomy trials, surgeons had to perform 25 procedures of each before being allowed to recruit into the RCT. Since the entire UK-REBOA Trial recruitment hung on whether the clinician deemed patients to be amenable to adjunctive treatment with REBOA, we acknowledge that it was probably unwise to have physicians inexperienced with REBOA recruiting patients since they would likely have no idea about whether patients would be “amenable” to treatment simply from completing a 2-day REBOA course (with “refreshers” as needed during a worldwide pandemic).
What they concluded:
“In trauma patients with exsanguinating hemorrhage, a strategy of REBOA and standard care in the emergency department does not reduce, and may increase, mortality compared with standard care alone.”
Really?
References:
- Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial. JAMA. Published online October 12, 2023. doi:10.1001/jama.2023.20850.
