Tag Archives: abstract

Head, Resuscitation

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

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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!

Reference:  PATIENTS WITH BOTH TRAUMATIC BRAIN INJURY AND HEMORRHAGIC SHOCK BENEFIT FROM RESUSCITATION WITH WHOLE BLOOD. EAST 2023 Podium paper #2.

Resuscitation

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

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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.

Reference: TRANSFUSION-RELATED COST COMPARISON OF TRAUMA PATIENTS RECEIVING WHOLE BLOOD VERSUS COMPONENT THERAPY. EAST 2023 podium abstract #28.

Research

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

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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!

Reference: STATISTICAL POWER OF RANDOMIZED CONTROLLED TRIALS (RCT) IN THE FIELD OF TRAUMA SURGERY. EAST 2023 podium abstract #6.

Abstracts, Outcomes

Best Of AAST 2022 #12: Angioembolization For Liver Injuries

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Solid organ injuries are relatively common from both blunt and penetrating mechanism due to the fact that the liver is the largest organ in the torso. Management of minor injury is relatively straightforward, but more complex injuries quickly become complicated. Unlike the spleen, there is no option to just “drop it in the bucket.” And recovery from high-grade hepatic injuries is fraught with issues like bleeding and bile leaks. These patients may take weeks or months to fully recover.

A wide variety of operative techniques for controlling liver bleeding were developed in the 1900s. These became a little less relevant late in the century with the addition of angiography and embolization to our suite of management techniques. Remember, angioembolization does not replace operative management, which is mandatory in unstable patients. But it can certainly help control bleeding and may reduce the need to operate early.

The group at Johns Hopkins hypothesized that angioembolization (AE) improves survival in patients with severe hepatic injuries. They collected data from 29 trauma centers in an AAST multicenter study. It focused on adult patients with Grade III-V injury from either blunt or penetrating mechanism. The data were sliced and diced by mechanism and type of management. There were three management possibilities: nonop management with or without AE, operative management with AE before or after, and operative management alone.

Here are the factoids:

  • A total of 1,697 blunt and 733 penetrating liver injury patients were studied with similar median ISS
  • As expected, higher ISS and blood transfusion > 6u was significantly associated with higher mortality
  • In the blunt injured patients managed nonoperatively, there was no association between mortality and use of AE although the p value was 0.056
  • Similarly, blunt trauma patients who underwent an operation and had AE either before or after had no difference in mortality (p value 0.09)
  • There was a significant survival advantage if AE was added to nonoperative management

The authors concluded that angioembolization does not improve survival in most severe liver injury cases with the exception of high-grade penetrating injury.

Bottom line: This abstract focuses on survival advantage from the use of AE. However, I think most trauma professionals actually use it as an adjunct to make other management (operative or nonoperative) easier. So I’m not surprised that they didn’t find much positive to say except in the case of penetrating injuries.

I also worry that the p values for both groups of blunt patients (operative + AE, nonop + AE) were very close to significance. Any time a study provides a negative conclusion because significance was not reached, I want to be sure it had the statistical power to detect it in the first place. With p values of 0.09 and 0.056, could a few more patients in each group have achieved statistical significance?

I don’t see that this abstract could (or even should) change our practice in the use of AE. I suspect that it does have an impact on complications, and it may help us stay out of the abdomen in severe cases where opening it could result in uncontrollable bleeding.

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

  1. Did you do a power analysis to determine if you could actually show a significant difference in the blunt patients? Although you had 1,697 total blunt patients, we do not know how many were in the operative vs nonop groups and the AE vs no AE subset of the nonop management group.
  2. Were there any differences in the ISS, age, or other demographics in the pre vs post or AE/no AE blunt subsets that might reveal some selection bias for patients undergoing in one subset vs the other? Since this is pooled data from many trauma centers, each surgeon determines if AE is used and when. It becomes very important to try to identify other factors that may explain your results.
  3. Do you recommend any changes in clinical care based on these results? What needs to be done to definitively answer the question?

This is interesting preliminary work, but I believe it needs additional refinement before we learn enough to change our current practice.

Reference: AAST MULTICENTER STUDY: DOES ANGIOEMBOLIZATION IMPROVE SURVIVAL FOR SEVERE HEPATIC INJURIES? AAST plenary paer #51, AAST 2022.

Abstracts, Complications

Best Of AAST 2022 #11: Trauma And The Gut Microbiome

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You know I don’t usually write about animal studies. I’m going to break that rule today to review an abstract that addresses what I think is an under-appreciated contributor to outcomes in trauma. The gut microbiome describes the collection of all genomes from microorganisms found in a particular environment. These genomes include bacteria, viruses, and fungi and can be found on all external surfaces of humans.

And I use the term “external” loosely. It includes the areas of the human body that are obviously exposed to the environment, but also areas where our body is wrapped around yet still separate from the it, such as the aerodigestive tract and vagina.

We are beginning to recognize the importance of the micro-organisms that inhabit these areas. They aid in digestion, fine tune the immune system, and synthesize proteins, amino acids, and vitamins that are essential to our health to name a few key tasks.

Many things can disrupt the microbiome including disease, diet, stress, and antibiotics. Previous work has shown that the microbiome changes throughout the hospital stay after trauma. Beneficial species tend to die out, and the ratio of pathologic vs beneficial species tilts toward the dark side.

The group from the University of Florida studied the effects of trauma and chronic stress in a group of rats to study the impact on the gut microbiome. One group of rats was subjected to a polytrauma model including pulmonary contusion, shock, cecectomy, and femur fractures. Another received the polytrauma treatment plus two hours of restraint stress daily. These groups were compared to an untreated control group. Gut flora were measured at baseline and on days 3 and 7.

Here are the factoids:

  • As expected, the microbiomes were similar across all groups at baseline
  • Polytrauma caused a significant change in bacterial diversity at both days 3 and 7 with both Bacteroides and Enterococcus prevalent
  • Polytrauma plus stress also depleted “good bacteria” and was associated with a switch to predominantly Enterococcus colonization

The authors suggested that the observed transitions to a pathologic microbiome may influence outcomes after severe trauma and critical illness.

Bottom line: I wanted to highlight this simple study because it relates to a similar topic that is exploding in the clinical nutrition field. The gut microbiome is being recognized as a key element of our overall health. However, it is very sensitive to external events and can be “knocked out of whack” by stress, trauma, bad diet, and even a single dose of antibiotics. Its derangement is recognized as a major factor in the development of C Difficile colitis.

This simple little rat study confirms that major trauma and stress negatively impact the animals’ microbiome. It did not examine outcomes, so no associations can be made here. Any such associations would not be directly applicable to humans, anyway. But it should serve to stimulate some thought and additional human studies to continue investigation in this field.

I have been struck by how we mistreat the gut microbiome in hospitalized patients through my own clinical observations over the years. A short course of antibiotics has been shown to severely impact the diversity of gut flora within days, and may require a year or more to recover back to baseline.

Extended fasting exhausts the food supply for the bacteria which may lead to the use of the gut lining for food, creating additional pathology. The composition of the nutritional supplements used in hospital are formulated from cheap ingredients which have been shown to disrupt the microbiome. Then add on trauma and chronic stress. It’s a terrible combination, yet we see it every day in hospitalized patients!

I predict that we will learn to pay more attention to all our various microbiomes in the future. A more thorough understanding may allow us to reduce complications (think C Diff) and might help us recognize some subtle factors that are contributing to overall mortality. 

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

  1. The audience will not be familiar with the microbiome diversity measures described in the abstract. Please take a little time to explain it, what is normal, and what happens when it changes.
  2. Were there any obvious outcome correlations observed that were not reported?
  3. Where do you go from here? Any plans for human studies on this topic?

As you can see, I find this area fascinating and believe that it is an underappreciated source of outcome variability in the patients we take care of. Figuring this out will help us tweak and optimize our overall patient care.

Reference: MULTICOMPARTMENTAL TRAUMATIC INJURY AND THE MICROBIOME: SHIFT TO A PATHOBIOME. Plenary paper #54, AAST 2022.