In The Next Trauma MedEd Newsletter: Interesting Stuff

The January issue of the Trauma MedEd newsletter will be sent out soon! It’s chock full of general stuff of interest to all you trauma professionals.

This issue is being released Sunday evening. If you sign up any time before then, you will receive it, too. Otherwise, you’ll have to wait until it goes out to the general public at the end of next week. Click this link right away to sign up now and/or download back issues.

In this issue, get some tips on:

  • Nonsurgical Admissions And The Nelson Score
  • Tip: Evaluation of Hematuria in Blunt Trauma
  • Central Lines Cause Hypercoagulability?
  • Lab Values From Intraosseous Blood
  • Leukocytosis After Splenic Injury

As always, this month’s issue will go to all of my subscribers first. If you are not yet one of them, click this link right away to sign up now and/or download back issues.

Cool Discovery: Bones Have Lymphatics!

The lymphatic system is a network of vessels that helps regulate fluid homeostasis, waste clearance, and immune response. Most tissues in the body have some type of lymphatic drainage. The main holdouts have been the brain, the eyes, and our bones.

Ten years ago, the brain lymphatic system (called glymphatics since they are associated with neuroglial cells) was discovered. This system is critically important to brain health. During deep sleep, our neurons shrink in size, allowing CSF to flush through the glymphatic system. This sweeps the accumulated debris (including tau and beta-amyloid) out through the glymphatics to be disposed of.

In 2014, Schlemm’s canals in the eye were also identified as functioning as a lymphatic system. These collect the aqueous humor absorbed by the trabecular meshwork on the surface of the iris.

And now, the Institute of Molecular Medicine at Oxford has discovered a lymphatic network in our bones! As anybody who has played with a microscope can attest, it’s easy and fascinating to view soft tissues. But working with calcified tissue is very challenging. For this reason, the organization of blood vessels in bone has been difficult to observe.

The authors used light sheet fluorescence microscopy to image intact bone specimens. This technique shines a sheet of laser light through a labeled specimen. A fluorescence detector perpendicular to the sheet of light records light output from the tagged items of interest in one two-dimensional layer. This technique can actually be used in living specimens, although in this study the bones were prepped and the calcium was carefully removed.

The authors identified lymphatics in mouse and human bone specimens. They also found that these lymphatics expanded in response to stress, which resulted in formation of more lymphatics. This, in turn, induced regeneration of the bone itself and hemopoietic cells in the bone marrow. However, as the animals aged, their lymphangiogenesis lessened, which may explain why bones in the elderly do not heal as well or as quickly.

Bottom line: This is an exciting discovery using a novel imaging technique. It showed not only the structure of these lymphatics but also their role in healing from injury. It raises the interesting possibility that manipulating the lymphatic endothelial cells might allow us to accelerate healing after injury.

First, we had lymphatics. Then, when they were found in the brain, we called them “glymphatics.” So now I will take the prerogative to name the ones discovered in bone as “blymphatics.” Not very sexy, but you get the idea!

Reference: Lymphatic vessels in bone support regeneration after injury. Cell. 2023 Jan 19;186(2):382-397.e24. doi: 10.1016/j.cell.2022.12.031. PMID: 36669473.

Best Of EAST 2023 #12: VTE Prophylaxis In Severe TBI

Time for another abstract on venous thromboembolic disease (VTE) prophylaxis, but this time in patients with severe head injury. VTE is a significant problem for trauma patients. Those with a potential source of bleeding from their injuries cause us to hesitate and consider the timing of chemical prophylaxis closely. Do we really want to cause more bleeding?

This is particularly problematic with intracranial hemorrhage, as the treatment is major brain surgery. Over recent years, the literature has been leaning toward earlier prophylaxis as soon as the intracranial blood has stopped evolving.

The EAST Multicenter Trials Group performed a seven-year retrospective review at 24 Level I and II trauma centers to assess the safety and efficacy of VTE chemoprophylaxis.  They divided patients into three groups: no prophylaxis, early prophylaxis (within 24 hours), and late prophylaxis (after 24 hours).

The authors assessed two endpoints: VTE occurrence and expansion of intracranial hemorrhage (ICH). They used several regression models to check their hypotheses.

Here are the factoids:

  • A total of 2,659 patients met the inclusion criteria. This averages out to 15 eligible patients per month per center. This is probably reasonable when combining a few high-volume centers with more lower volume centers.
  • Compared to early prophylaxis, patients who received late prophylaxis were twice as likely to develop VTE, although this was not statistically significant (p = 0.059)
  • Compared to early prophylaxis, patients who received no prophylaxis were a third less likely to develop VTE, although this, too, was not statistically significant (p = 0.39
  • About 25% of patients who received either early or late prophylaxis suffered an extension of their ICH, but only 17% of the no-prophylaxis group did
  • The regression model showed that the no prophylaxis group was 36% less likely to develop ICH extension compared to either early or late prophylaxis groups.

The workgroup concluded that the development of VTE was not dependent on the timing of the start of prophylaxis. Furthermore, patients who did not receive any prophylaxis had significantly decreased odds of ICH extension. The group recommended larger randomized studies to extend this work.

Bottom line: Shocker! This multicenter study suggests that the no prophylaxis and early prophylaxis groups had fewer VTE events than the late group, although these results were not statistically significant. This means that there wasn’t an advantage to giving the shot.

And the other major conclusion was that both early and late prophylaxis was associated with a significantly higher incidence of ICH extension. 

Roll these together, and you will find that neither early nor late prophylaxis help prevent VTE, yet they are both associated with additional bleeding in and around the brain! 

Heresy! I am trying to figure out what to make of these results. Perhaps the retrospective nature of the study and the wildcards this introduces influenced the results. It could be a study power problem, except the numbers were approaching significance that was unfavorable for prophylaxis.

I will be very interested to hear how the authors explain these findings. And yes, a well-powered randomized study would be great, but I don’t think many institutional review boards will be keen on a no-treatment group given our current fear of VTE. So don’t count on any real answers soon.

Reference: EARLY VTE PROPHYLAXIS IN SEVERE TRAUMATIC BRAIN INJURY: A PROPENSITY SCORE WEIGHTED EAST MULTICENTER TRIAL. EAST 2023 Podium paper #38.

Best Of EAST 2023 #11: Prehospital Use Of TXA

More stuff on TXA! I published two posts back in December on TXA hesitancy. This Friday, the trauma group at Wake Forest is presenting an abstract on TXA use by prehospital trauma professionals.

It is very likely that EMS carries tranexamic acid (TXA) in your area. Each agency has its own policy on when to administer, but the primary indication is hemorrhagic shock. A few ALS services may infuse for serious head injury as well.

The Wake Forest group was concerned that TXA administration might be occurring outside of the primary indication, hemorrhagic shock. They reviewed their experience using a six-year retrospective analysis of their trauma registry. The patients’ physiologic state before and after arrival at the hospital was assessed, as were the interventions performed in both settings.

Here are the factoids:

  • Of 1,089 patients delivered by 20 EMS agencies, one-third (406) had TXA initiated by EMS
  • Only 58% of patients who received prehospital TXA required transfusion after arrival
  • TXA administration based on BP criteria were as follows:
  • Similar compliance was noted when examining only high-volume EMS services

The authors concluded that TXA use is common in the prehospital setting but is being used outside of literature-driven indications.

Bottom line: This is an interesting snapshot of TXA use surrounding a single Level I trauma center. As such, it can’t be automatically applied to all. However, my own observations suggest that this drug is being used more liberally nationwide.

Clearly, the prehospital providers are starting TXA on patients who do not fit the category of severe hemorrhagic shock. Only 30% of patients receiving it had SBP < 90. Is this a bad thing? Referring back to my conversation on TXA hesitancy, I think not. But do keep in mind that giving any drug when not indicated adds no benefit and can certainly increase risk. The good news is that TXA is very benign when it comes to side effects.

However, policies are designed for a reason: safety. And if the EMS agency policy says to give TXA only for SBP < x, then that’s when it should be given. The prehospital PI process (or the trauma center’s) should identify variances and work to correct them. If EMS is “overusing” TXA in your area, your trauma center should add this as a new prehospital PI filter and let them know when it happens.

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

  • Is using the need for transfusion a valid measure of the need for TXA? You found that half of the patients receiving TXA were not transfused. The decision to transfuse depends on surgeon preference, and they don’t always use objective criteria. And hey! Maybe the TXA worked, obviating the need for blood!

This is a straightforward and intriguing paper. I’m excited to hear more details on how you sliced and diced this data.

Reference: ARE DATA DRIVING OUR AMBULANCES? LIBERAL USE OF TRANEXAMIC ACID IN THE PREHOSPITAL SETTING. EAST 2023 Podium paper #34.

Best Of EAST 2023 #10: Early VTE Prophylaxis In Adolescents With Solid Organ Injury

Chemoprophylaxis against venous thromboembolism (VTE) is routine in trauma care. In most cases, it can be initiated shortly after admission in most trauma patients. However, there are a few major exceptions, including eye injuries and brain injuries with intracranial hemorrhage.

Solid organ injury used to be cause for concern when considering prophylaxis, but most trauma centers are now comfortable beginning within 24 to 48 hours after injury. Having said that, those numbers are for adult patients. What about the younger ones?

The University of California Irvine group queried the TQIP database (3 recent years) to examine outcomes for adolescent patients (12-17 years old) given VTE prophylaxis after injury to liver, spleen, and/or kidney. They excluded patients who had TBI, anticoagulation or coagulopathy, immediate laparotomy, transfers in, and patients who died or were discharged within 48 hours. They matched patients for age, comorbidities, grade of injury, overall severity of injury, and hypotension/need for transfusion.

Eligible patients who received chemoprophylaxis early  (within 48 hours) vs. late were reviewed to identify any differences in complications, length of stay, failed non-op management, and mortality.

Here are the factoids:

  • A total of 1,022 cases were isolated from the TQIP database, and 417 adolescent cases were matched to adults
  • VTE rate was statistically the same, 0.6% in the early group vs. 1.7% in the delayed group
  • Failed non-op management was identical at 5.9% vs. 5.6%
  • There was one death in the delayed group and none in the early group (not significant)
  • ICU LOS was the same at 3-4 days
  • One item not mentioned in the body of the abstract: hospital length of stay was significantly longer in the early group: 9 days vs. 6 days

The authors concluded that early VTE prophylaxis in adolescent trauma patients did not increase failure of nonoperative management, nor did it decrease the incidence of VTE.

Bottom line: This is a study that needed to be done. Due to IRB restrictions, it is typically more challenging to perform actual studies on children and adolescents. Retrospective use of databases helps overcome this problem, although it always introduces a few unwanted wrinkles.

We frequently assume that adolescents behave physiologically like adults. Although often true, you can’t always count on it. Those of us who take care of children and young adults know that they tend to do better than adults by most measures. But again, this is an assumption and needed to be studied.

This database study was limited to three years of data and only produced 417 matched cases for study. This is a small number, and I always worry about statistical power. If the results of such a study are negative, one is left wondering if a proper power analysis was done.

One puzzling result left me wondering about the power question. Patients who received early prophylaxis had exactly the same rate of VTE as those who received it late. Adult data indicates that early use should decrease this complication. Is this another indication of a statistical power problem? Would the inclusion of more patients have shown a real difference?

The other result that struck me (and was not commented upon in the body of the abstract) was the statistically significant 50% increase in hospital length of stay for the early prophylaxis group. Is there some unknown variable that was not matched that caused it? This is one of the known pitfalls of these retrospective database studies.

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

  • Broken record question: Did you have enough cases to provide adequate statistical power? This study showed a negative result. Did you have enough matched cases to actually be able to detect a difference if there was one? Why not add a few more years of data and recalculate?
  • How do you explain the failure of early VTE prophylaxis to protect these patients from DVT or PE? Is this also a statistical power problem?
  • Why is the hospital length of stay significantly longer in the early prophylaxis group?

This intriguing paper follows my bias toward treating these patients exactly the same as adults with early chemoprophylaxis. I just need a few of the loose ends tied up.

Reference: SIMILAR RATE OF VENOUS THROMBOEMBOLISM AND FAILURE OF NON-OPERATIVE MANAGEMENT FOR EARLY VERSUS DELAYED VTE CHEMOPROPHYLAXIS IN ADOLESCENT BLUNT SOLID ORGAN INJURIES: A PROPENSITY-MATCHED ANALYSIS. EAST 2023 Podium paper #27.