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Abdomen

Trauma And The Gut Microbiome

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This is a follow-on post from one published last week (gut microbiome changes in rats due to trauma). Click here to read it.

One of the newest frontiers in health-related research recognizes the importance of the human microbiome. This term describes the collection of all genomes from the microorganisms found in a particular environment, such as in, on, or around a human. The term microbiota refers to the specific bacteria, viruses, and fungi that colonize the areas within this environment.

Within the last decade or so, we have just begun to appreciate the importance of the microorganisms that live within us. From a purely numerical standpoint, there are 10 times as many of them as there are our own human cells. However, since they are so small in comparison, we can’t really appreciate the huge number of “other” cells in and on us.

These tiny cohabitants provide many, many functions that are important to our health and well-being. They protect us from pathogenic organisms, help digest our food, fine-tune our immune system, and synthesize proteins, amino acids, and vitamins that are essential to our health. And much more!

The usual microbiota can be disrupted by disease, poor diet, stress, and even a single dose of antibiotics. With each new research paper, we recognize new functions for and disruptors of our microbiota.

The surgery groups at two San Antonio hospitals, UT Health and the US Army Institute of Surgical Research, recognize the importance of the gut microbiota, building upon prior work demonstrating changes within it in the presence of trauma and burn injury.

The authors performed a prospective, observational cohort study of severely injured patients over a two-year period. They attempted to characterize differences in the microbiota between trauma patients and to identify changes in these communities over time.

A rectal swab was obtained from each patient shortly after admission and the microbial DNA present was identified. This was repeated regularly throughout the hospital stay.

Here are the factoids:

  • 72 patients and 13 healthy controls were enrolled
  • Patients were severely injured with a mean ISS of 21; an average of 6 units of blood products were given in the first 24 hours
  • Only one fourth of the injured patients had a microbiome similar to the healthy controls
  • These 26% received significantly more blood products than the dissimilar patients (14 units vs 3)
  • There were significant decreases in the numbers and ratios of normal gut bacteria and increases in the numbers of pathogenic bacteria. These changes increased with time in hospital

Bottom line: Yes, this is new and bizarre territory. It appears that shock, hypoxia, medications (and not just antibiotics), surgical intervention, and poor nutrition can adversely affect the microflora in our gut. Conversely, early transfusion seems to ameliorate this effect to some degree.

At this point in time, there is nothing you can do with this knowledge. Just be aware that everything you routinely do to your patients can change their microbiota, and this may in turn have unexpected effects on their health and recovery. I anticipate seeing many more papers like this one in the near future.

Reference: A prospective study in severely injured patients reveals an altered gut microbiome is associated with transfusion volume. J Trauma 86(4):573-582, 2019.

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.

Abstracts, Technology

Best Of AAST 2022 #10: REBOA For Pelvic Fractures

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Papers for Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) use in trauma patients have been accumulating for the past decade or so. There are three zones within the aorta, and the REBOA balloon can be inflated in either Zone II for abdominal vascular injuries or Zone III for pelvic bleeding. Here’s a nice diagram for reference:

The original studies focused on Zone II deployments, but over the past five years or so there has been growing focus on using REBOA in Zone III. Pelvic arterial bleeding can be quite problematic, and if the patient is hypotensive in the emergency department, it is not permitted to take them to interventional radiology for management. The only choice is a trip to OR for preperitoneal packing or some less effective procedure.  With the use of Zone III REBOA, it became possible to stabilize vital signs and then allow transport to IR or hybrid OR for angioembolization.

After the initial rush of very positive research, more recent papers are a bit more tempered with results that are not as cut and dried. This abstract from Hartford Hospital attempts to add a bit more information about the use of Zone III REBOA in patients who required a hemorrhage control procedure. The authors performed a retrospective review of four years of TQIP data. They compared outcome data in hypotensive adult patients with pelvic fractures requiring some type hemorrhage control procedure. The authors divided patients into REBOA+ and REBOA- groups, and looked at mortality, blood utilization, lengths of stay, and REBOA complications.

Here are the factoids:

  • Of the 4,453 patients who met inclusion criteria, only 139 patients underwent Zone III REBOA
  • The REBOA+ patients had lower BP and GCS and ISS was higher prompting the use of propensity matching
  • In order to equalize comparisons patients were propensity matched the the variables listed above, yielding 121 pairs for study
  • In-hospital and 24-hour mortality were double in the REBOA+ group (50.5% vs 25% and 31% vs 14.3%, respectively)
  • Blood transfusion was also higher in the REBOA+ group (median 4L vs 1.75L)
  • AKI was higher in the REBOA+ group (16% vs 7%) but the amputation rates were the same (no numbers given)

The authors concluded that Zone III REBOA appears to have worse outcomes and suggest that more prospective studies are indicated.

Bottom line: I have been a REBOA skeptic for some time so I have to be careful not to feed my confirmation bias. Many of the previously published positive papers include authors who have a relationship with one of the major REBOA device manufacturers. Papers from centers without any conflicts of interest are generally less positive.

Despite my own bias I also have some major questions about this abstract. The biggest thing is that I can’t make the statistics work. Granted, the entire analysis is not in the abstract. But the mortality rates given in percentages don’t yield integers when multiplied by the 121 patients in each group.

This makes me worry that we are not seeing all the statistics and we are somehow getting relative risk rather than absolute risk. I’m also confused about why the SBP, ISS, and GCS matched groups would have a difference in AKI rates in addition to the mortality numbers. Are there other significant variables affecting morbidity and mortality that were not identified or controlled?

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

  1. Review the mortality calculations for us. How can you have a hospital mortality rate of 50.5% with 121 patients (= 61.105 people)? Provide the absolute mortality numbers so we can do the math.
  2. Why are the transfusion numbers so much higher in the REBOA+ group? Isn’t this device supposed to reduce bleeding? It seems unlikely that REBOA is making them bleed more. Is there something else going on?
  3. Similarly, why would AKI be higher in REBOA+ patients? The balloon is located below the kidneys and they should benefit from better perfusion.
  4. Could there be other factors not analyzed that contributed to the poorer outcomes in the REBOA+ group? What might they be?

I suspect the snapshot that the TQIP data allows may not be enough to let us see the entire picture here. I am looking forward to additional information during the presentation to help clarify these issues.

Reference: DOES THE USE OF REBOA IMPROVE SURVIVAL IN PATIENTS WITH PELVIC FRACTURES REQUIRING HEMORRHAGE CONTROL INTERVENTION? AAST Plenary paper #46, AAST 2022.

Abstracts, Thorax

Best Of AAST 2022 #9: Management Of Low Grade Blunt Thoracic Aortic Injury

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It has been interesting to watch the evolution of the treatment of blunt thoracic aortic injury (BTAI). In my training, patients with an abnormal mediastinal contour on chest x-ray were whisked away to interventional radiology for a thoracic aortic angiogram. Yes, there was no such thing as a CT scan for anything but the head! Here’s a sample chest x-ray:

I wrote a post 12 years ago describing the various findings of a blunt aortic injury, many of which are present above. You can the post by clicking here.

In the 1-2% where the angio was positive (yes, you read that right; we did a lot of negative angiograms) the patient was then whisked off to the OR for an open aortic graft via thoracotomy. The advent of CT scans of the torso and improving resolutions allowed us to be more selective with angiography. And finally as CT angiography matured, aortic angiography became a thing of the past.

Then came TEVAR about 20 years ago. There were some growing pains as we refined the technology, but now this endovascular procedure is the standard of care for most aortic injuries. While there was also a place for nonoperative management, it was really just maintaining a reasonably low blood pressure to protect the vessel while getting the patient into good enough condition to tolerate anoperation.

Now we are beginning to slice and dice treatment based on grade. Many centers have recognized that an intimal injury (Grade I) is only a very minor disruption to the inside of the vessel and does not make it more susceptible to rupture. Grade II management has been less clear. Here is a diagram of the various grades.

It makes sense that an invasive procedure may be less helpful for injuries that do not disrupt the layer of the vessel that provides its strength. But remember, common sense isn’t always the truth.

The group at Dell Seton Hall reviewed all patients with low grade BTAI (Grades I and II) in the Aortic Trauma Foundation Registry for a six year period. Their hypothesis was that these injuries could be successfully treated with medical management alone. They reviewed the data for mortality, complications, vent days, and lengths of stay.

Here are the factoids:

  • A total of 880 patients were enrolled and 274 had low grade injuries; 5 were then excluded when their lesion progressed and they underwent TEVAR
  • Of the 269 remaining patients, 81% were treated with medical management (81% Grade I, 19% Grade II) and the remainder with TEVAR (20% Grade I, 80% Grade II)
  • Rates of thoracotomy, craniectomy, and sternotomy were the same in both groups, but TEVAR patients were more likely to have a laparotomy (31% vs 15%)
  • Mortality was significantly higher in the TEVAR group (18% vs 8%) but the mortality from the aorta was not quite significant (4% vs 0.5%)
  • Complications (DVT and ARDS) were also significantly higher in the TEVAR group
  • Vent days and lengths of stay were equivalent

The authors concluded that medical management alone is safe and appropriate, with a lower mortality and decreased complications compared to routine TEVAR.

Bottom line: Hmm, color me skeptical. Remember, this is a registry study, so information tends to be limited outside the usual demographics and data points that are very pertinent to the purpose of the registry. The most important concept is that the patients in each group must be identical in every way except for the intervention.

We can try to make them as identical as possible by matching pairs or subgroups of patients. But the biggest problem is that the number of patient characteristics that might be important to match may not be available for analysis in the database.

When the patients were initially treated at contributing centers, there were no specific rules that the individual surgeons had to follow to decide between medical management and TEVAR. They could pick and choose based on their own experience. Could the surgeon have recognized some patients as higher risk and opted for TEVAR to make sure the aorta would not become an issue in conjunction with their other injuries? And unfortunately, perhaps that higher risk issue is what ultimately killed them and not the aorta. It’s basically a form of unhealthy user bias.

This abstract is an interesting tidbit that should push us to question whether medical management is better, at least in some subsets of low grade aortic injury patients. Then someone can perform a more robust study to confirm or refute its safety. Unfortunately, this may never happen due to the low incidence of this injury. It took six years to accumulate only 269 eligible patients in this registry!

Here are my questions for the authors and presenter:

  • What data points are actually in the registry? Specifically, is there fine detail about the other injuries the patient had? Could these have contributed to TEVAR mortality, or the selection of the patient for TEVAR to try to reduce the perceived mortality risk?
  • When you stated that there was “no difference in demographics or mechanism of injury” what were these, exactly?
  • What did patients actually die from in the Grade I and Grade II groups? Be more specific than “aortic-related” or not.
  • Do you have any worries about the five patients whose lesions progressed? When should patients be re-scanned to identify those who might benefit more from TEVAR?

This is a thought provoking abstract, and I am very interesting in hearing what the next steps should be.

Reference: MEDICAL MANAGEMENT IS THE TREATMENT OF CHOICE FOR LOW GRADE BLUNT THORACIC AORTIC INJURIES. Plenary paper #45, AAST 2022.