Best Of EAST 2023 #4: Whole Blood In Patients With Shock And TBI

We know that even a brief shock episode in patients with severe TBI dramatically increases mortality. Therefore, standard practice is to ensure good oxygenation with supplemental O2 and an adequate airway ASAP and to guard against hypotension with crystalloids and blood if needed.

Many papers (and several abstracts in this bunch) have been written about the benefits of whole blood transfusion. The group at the University of Texas in Houston compiled a prospective database of their experience with emergency release blood product usage in patients with hemorrhagic shock.

They massaged this database, analyzing a subset of patients with severe TBI, defined as AIS Head of 3. They specifically looked at mortality and outcome  differences between those who received whole blood and those who received component therapy.

Here are the factoids:

  • A total of 564 patients met the TBI + shock criteria, and 341 (60%) received whole blood
  • Patients receiving whole blood  had higher ISS (34 vs. 29), lower blood pressure (104 vs. 118), and higher lactate (4.3 vs. 3.6), all indicators of more severe injury
  • Initial univariate analysis did not identify any mortality difference, but using a weighted multivariate model teased out decreases in overall mortality, death from the TBI, and blood product usage
  • Neither statistical model demonstrated any difference in discharge disposition of ventilator days

The authors concluded that whole blood transfusion in patients with both hemorrhagic shock and TBI was associated with decreased mortality and blood product utilization.

Bottom line: This is yet another study trying to tease out the benefits of giving whole blood. The results are intriguing and show an association between whole blood use and survival. But remember, this type of study does not establish causality. It’s not possible to rule out other variables that were not available or not considered that could be the cause of the difference.

In this type of study, it’s essential to look at the design. Was it possible to create the study to record a complete set of variables that the researchers thought might contribute to the outcomes? Or is it a retrospective analysis of someone else’s data that contains just a few of them? This study falls into the latter category, so we have fewer data elements to work with and the likelihood that others that are not present could contribute to the outcomes.

The details of the multivariate analysis are also important. The authors stated that weighted multivariate analyses were performed. It’s not possible to provide details in a standard abstract, but these will be important for the audience to understand.

Here are my questions and comments for the presenter/authors:

  • Tell us more about the database you used for the analysis. What was the purpose? How many data elements did you collect, and how are they related to your research questions?
  • How did you decide which variables to include in your multivariate analysis? And how did you determine the weights? These can have a significant effect on your results.
  • This is a preliminary proof of idea study. How should this be followed up to move from association to causation?

This is just one of many exciting studies trying to shed light on the forgotten benefits of whole blood in trauma. I’m looking forward to seeing the final manuscript!


Best Of EAST 2023 #3: The Cost Of Whole Blood vs Component Therapy

Decades ago, blood banks discovered they could fractionate units of whole blood into components for focused use. This was useful for patients who were thrombocytopenic or needed specific plasma factors. But trauma patients bleed whole blood, and trying to reassemble whole blood from components does not work well. Have a look at this chart:

It all comes down to money. Blood banks found they could charge more for the sum of the components of a unit of whole blood rather than the one unit itself. But now, with whole blood in trauma becoming a thing again, it’s essential to reexamine costs.

The University of Texas at San Antonio group examined transfusion-related charges for trauma patients receiving either component therapy or low-titer O+ whole blood within six hours of arrival. This was a retrospective review of prospectively collected data. During the first two years, only component therapy was given. Whole blood was introduced during the last four years.

Here are the factoids:

  • Once the trauma center switched to whole blood, total annual transfusion charges, as well as component charges decreased by 17% overall
  • In both adults and children, whole blood was associated with a significantly lower cost per ml delivered and cost per patient throughout all phases of care
  • In severely injured patients (ISS>15), the same significantly lower costs were also noted
  • Patients who triggered the massive transfusion protocol also had a lower cost per ml of product in the ED and the first 24 hours

The authors concluded that whole blood was associated with lower charges and “improved logistics,” especially in massive transfusion patients.

Bottom line: This is an interesting and important paper. However, several questions still need to be answered. I recognize that there is limited space in an abstract, so I will list them below in hopes the authors will answer them during the presentation.

The first issue is that the numbers of patients and quantities of blood products given need to be listed. These are very important because the figures list only total charges and maybe costs. These numbers are not per unit of product, so the data may be skewed if the number of patients was different between the groups. For example, if 100 patients received component therapy and only 10 got whole blood, costs or charges could definitely be skewed.

And then there is the cost vs. charge confusion. The abstract seems to use them interchangeably. The methods section of the abstract states that charges were analyzed. Yet cost is mentioned in the results, and figure two shows “cost” on the axes, but the caption states that charges were listed. 

We all know that hospitals can charge whatever they like, and that amount may vary based on insurance and other factors. The relationship between the charge and the cost is tenuous at best. Hopefully, the authors will clarify this at the start of the presentation.

Here are my comments and questions for the presenter/authors:

  • Please clarify the concept of charges vs. costs at the presentation’s beginning. If you truly analyzed only charges, do they bear any relationship to the actual costs of the units?
  • Shouldn’t your analysis of annual “charges” for product expenditures in Figure 1 be per unit? Otherwise, the costs and charges could be lower if fewer products were given after whole blood was introduced.
  • Was the switch to whole blood absolute, or was component therapy still given in some cases after 2018? If the switch was not total, there could be a selection bias in patients who received whole blood.
  • Figure 2 also appears to be total charges (or costs), not per patient or unit. But, again, without numbers it is difficult to say if the dollar differences are significant.
  • What are the “improved logistics” mentioned in the conclusion section? And how could they lower charges (or costs) in your study?

Lots of questions. I think you will need to provide a lot of explanation up front to justify your findings. Nevertheless, I’m excited about the presentation.


Best of EAST 2023 #2: REBOA In Cardiac Arrest

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) remains one of the shiny new trauma toys. Yet, with nearly a decade of human study, we are still struggling to define the right patients to benefit from it.

A group of REBOA superfans sought to perform a secondary analysis of a research database from the US Department of Defense of patients at six Level I centers in the US. It contained outcomes of patients in hemorrhagic shock due to non-compressible bleeding below the diaphragm. The authors analyzed the subset of patients who presented in cardiac arrest and underwent either REBOA or resuscitative thoracotomy (RT).

Here are the factoids:

  • There were 454 patients in the database, and 72 underwent either REBOA or RT
  • REBOA patients were significantly older (46 vs. 35 years) and were more commonly victims of blunt injury (81% vs. 46%)
  • AIS for abdomen was lower in the REBOA group, but AIS head and chest were the same
  • Times from arrival to aortic occlusion and to procedure completion were significantly longer in the REBOA group
  • REBOA patients received more red cells and plasma in the ED, but 24-hour transfusions were the same
  • Mortality was the same between REBOA and RT, and did not change even after some statistical magic

The authors concluded that REBOA was not associated with a survival or transfusion advantage in patients already in arrest.

Bottom line: I was amazed to see a negative result from a group who tend to be avid REBOA cheerleaders. And although the abstract conforms to my own bias about REBOA, there are several things to consider here. 

First, the sample size is very small. A total of 72 patients from the database fit the cardiac arrest on arrival criterion. There is also no information on prehospital arrest duration for the patients.  The dead tend to stay dead despite just about any intervention.

Here are my questions for the presenter and authors:

  • Have you performed a power analysis to determine how many patients were needed to show real differences between the groups? Were you getting close with the 72, or a lot more needed?
  • Also, you did not break down how many of the 72 patients were in the REBOA vs RT groups. Please provide those numbers.
  • Were you able to determine how long the patients had been in arrest before arrival? This could definitely influence survival rates.
  • Did you analyze the subset of survivors in each group? You noted that times to procedure start and completion were longer with REBOA. Did the survivors get to aortic occlusion sooner? Could you identify any subjective factors that seemed associated with their survival?

I wouldn’t get too depressed yet about the efficacy of REBOA in these patients. This study just tells us that REBOA is not a miracle cure for cardiac arrest, but we can still continue to learn more about this device and which patients it is best suited for.



Best Of EAST 2023 #1: The Quality Of Trauma Research

I’ve been reading and reviewing scientific papers for years. One of my biggest pet peeves is the preponderance of studies that have been thrown together with insufficient thought given to research design. One of the most common issues I see in any study is the failure to look at study size and statistical power. The biggest offenders are the underpowered non-inferiority studies that claim two choices are equally valid when there were never enough subjects to show a difference in the first place!

If you want to see this in action, look at the studies that justify the “small chest tube is not inferior to bigger chest tube” studies.

But I digress. The first EAST abstract, I will discuss critically examined randomized clinical trials (RCT) relating to trauma published over ten years. The authors, from the Ryder Trauma Center in Miami, reviewed these studies for type (superiority, inferiority, equivalence), sample size calculation, and power analysis.

Here are the factoids:

  • Only 118 randomized clinical trials were identified in 20 journals over the ten years (!!)
  • Only half were registered before performing the research
  • Most were equivalence studies (49%)
  • Only half had performed a sample size calculation first, and only half of those actually met their target enrollment (!)
  • 70% of studies had a positive result
  • Overall, only about one-third to one-half of studies were adequately powered to show an effect size

The authors concluded that a large number of RCTs either did not perform a sample size calculation in advance, did not meet their enrollment targets, and weren’t powered enough to detect even a large effect.

Bottom line: Unfortunately, this abstract confirms my informal bias based on reading numerous papers over the years. There is a lot of weak research being published. And this applies not only to the field of trauma but to all scientific work.

There is a tremendous amount of pressure to publish. Those at academic institutions must be productive to keep their job. And the American College of Surgeons Verification Review Committee requires Level I trauma centers to publish twenty papers in peer-reviewed journals every three years. 

Unfortunately, this pressure pushes trauma professionals to come up with weak ideas that may not be well supported statistically. And there is an implicit bias in research publications that rewards positive results. This can be seen in this abstract’s 70% positive result rate. It’s boring to read a paper that shows that some new approach truly didn’t have an appreciable effect. But knowing this fact may help other researchers in the field avoid duplicating ineffective interventions.

This is an important abstract that clearly points out the shortcomings in published randomized controlled trials. But what about the 95+ percent of papers that do not use such a rigorous study design?

Here are my questions/comments for the presenter and authors:

  • Please provide the denominator of all the studies you reviewed. Only 118 were RCTs, which is woefully low. Please give us an idea of how many less rigorous studies were published over the ten-year study period.
  • Were there any obvious geographical patterns in study quality? Were RCTs from any specific continent of higher quality from the sample size perspective than others?

This important abstract is needed to stimulate more thought and interest in publishing better papers rather than more papers!