Tag Archives: DVT

Complications

Predicting VTE Risk In Children

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There’s a lot of debate about if and at what age injured children develop significant risk for venous thromboembolism (VTE). In the adult world, it’s a little more clear cut, and nearly every patient gets some type of prophylactic device or drug. Kids, we’re not so certain about at all.

The Children’s Hospital of Wisconsin tried to tease out these factors to develop and implement a practice guideline for pediatric VTE prophylaxis. They prospectively reviewed over 4000 pediatric patients admitted over a 6 year period.

It looks like the guideline was developed using some or all of this data, then tested using regression models to determine which factors were significant. The guideline was then tweaked and a final model was implemented.

Here are the factoids:

  • 588 of the patients (14%) were admitted to the ICU, and 199 of these were identified as high-risk by the guidelines
  • Median age was 10 (this is always important in these studies)
  • VTE occurred in 4% of the ICU patients, and 10% of the high-risk ones
  • Significant risk factors included presence of central venous catheter, use of inotropes, immobilization, and GCS < 9

Bottom line: This abstract confuses me. How were the guidelines developed? What were they, exactly? And the results seem to pertain to the ICU patients only. What about the non-ICU kids? The abstract just can’t convey enough information to do the study justice. Hopefully, the oral presentation will explain all.

I prefer a very nice analysis done at the Oregon Health Science University in Portland. I wrote about this study earlier this year. The authors developed a very useful calculator that includes most of the risk factors in this model, and a few more. Input the specific risks, and out comes a nice score. The only issue is, what is the score threshold to begin prophylaxis and monitoring? Much more practical (and understandable) than this abstract. Check it out at the link below.

References:

  1. Evaluation of guidelines for injured children at high risk for venous thromboembolism: A prospective observational study. J Trauma Acute Care Surg. 2017 May;82(5):836-844.
  2. A Clinical Tool for the Prediction of Venous Thromboembolism in Pediatric Trauma Patients. JAMA Surg 151(1):50-57, 2016.
Newsletter

The March Issue Of The TraumaMedEd Newsletter Is Available!

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The March issue of the Trauma MedEd newsletter is now available to everyone!

It’s chock full of general stuff of interest to all you trauma professionals.

In this issue, you will learn about:

  • Should I Apply Compression Devices To Patients With Known DVT?
  • Why Do They Call It The Surgical Neck Of The Humerus?
  • You’ve Been Pimped!
  • Nursing: When Is Drain Output Too Bloody?

To download the current issue, just click here! 

Or copy this link into your browser:  https://www.traumameded.com/courses/popular-topics/

This newsletter was released to subscribers a week ago. If you would like to be the first to get your hands on future newsletters, just click here to subscribe!

Pharmacy

How Early Can We Start Chemoprophylaxis In TBI Patients?

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We’ve learned a couple of things in the last two posts by reviewing recent systematic review / meta-analysis studies. First, low molecular weight heparin provides better prophylaxis against venous thromboembolism (VTE) than unfractionated heparin. And giving prophylaxis within the first 72 hours of admission significantly decreases the incidence of VTE with no increase in existing intracranial bleeds or mortality.

So the only remaining question is, how low can you go? That is, how soon can you safely start chemoprophylaxis? The trauma group at George Washington University in DC put together a study to examine this question.

They, and one other Level I trauma center, performed a retrospective cohort study of adult, blunt TBI patients over a three year period. Patients with penetrating brain injury, and those with any other body region with significant injury (AIS >1) were excluded so this group truly represented isolated brain injury. Other exclusion criteria were progression of blood on CT within 6 hours, and crani or death within 24 hours. Early VTE prophylaxis was defined as occurring within 24 hours, and late was > 24 hours.

All patients had hourly neuro evaluations and a repeat head CT at six hours after admission. All had compression devices applied to their legs, and received either low molecular weight (LMWH) or unfractionated heparin (UH) at a fixed dose regarding of body habitus. Anti-Factor Xa levels were not measured.

Here are the factoids:

  • Between the two centers, 264 met inclusion criteria
  • About 40% received early prophylaxis and the remaining ones received their drug after 24 hours
  • ISS was higher (18 vs 15) and GCS was lower (13 vs 14) in the late therapy group
  • About 88% of patients in the early prophylaxis group received LMWH vs only 63% in the late group
  • Average time to prophylaxis start in the early group was 17 hours vs 47 hours in the late group
  • There were no differences in bleed progression between early and late groups (5.6% vs 7%)
  • The craniotomy / craniectomy rates were the same in early and late groups (1.9% vs 2.5%)
  • VTE rate was the same in early vs late groups (0% vs 2.5%)

Bottom line: The authors concluded that there was no additional risk in giving early VTE prophylaxis in TBI patients with a stable CT seven hours after arrival. This was true for patients with subdural, epidural, subarachnoid, and intraparenchymal bleeds.

But there are some limitations to consider. This was a retrospective study, and was a “how we do it” study” as well in terms of the choice of LMWH vs UH. This means there was not protocol for the form of heparin used; that was determined by surgeon preference. 

There was also a difference in ISS and GCS between groups. However, the difference may not have been clinically significant, and it could have made the late group look worse if it were. Statistically, it did not.

And finally, the numbers are small and there was no power analysis. So there is the question of whether a significant difference could have even been detected.

What does it all mean? Well, it suggests that early (within 24 hours) chemoprophylaxis does not cause harm compared to later administration. But the study is not definitive enough to change practice yet. It should definitely prompt discussions and practice guideline development for starting prophylaxis after 24 hours of CT scan stability now. And hopefully these authors (or others) are planning a better prospective study to help us start even sooner!

Reference: Early chemoprophylaxis against venous thromboembolism in patients with traumatic brain injury. Am Surgeon 88(2):187-193, 2021.

Pharmacy

Early vs Late Chemoprophylaxis In Patients With Intracranial Hemorrhage

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In my last post, we looked at our knowledge base regarding the use of unfractionated heparin versus low molecular weight heparin. And the latter won. Today, let’s dig into the question of early versus late prophylaxis in patients with TBI and intracranial hemorrhage.

Neurosurgeons are remarkably cautious when considering anticoagulant thromboprophylaxis in these patients. Obviously, there is always concern for making the bleeding worse. This is very undesirable where there is little extra space and drainage is complicated.

But as we know, dogma about these issues tends to get spread very easily, with little scientific support. Let’s review another systematic review and meta-analysis (see last post) that examines the question.

As is usual, there have been a lot of contributions to this area over the years. Unfortunately, many are not entirely related to the question or have significant bias or design flaws. Of a total of 1,490 papers identified by the authores during PubMed searches only 29 were on topic. And of these only 11 were suitable for analysis. Early prophylaxis was defined as within 72 hours, although the authors were able to slice and dice this into shorter intervals.

Here are the results:

  • Progression of hemorrhage. There was no significant progression of intracranial bleeds seen at 24, 48 or 72 hours. However, this result is probably somewhat biased by the fact that fewer patients with severe injury are enrolled in studies of VTE prophylaxis. The overall odds ratio for early vs late administration was 0.86 favoring early prophylaxis. However, the confidence interval crossed the midline, so there was no difference noted in progression of bleed or mortality with early VTE prophylaxis.
  • Occurrence of DVT. Many of the studies indicated a decrease in VTE in the patients given early prophylaxis. This was noted at all three time intervals as well. The overall odds ratio was 0.58, which was statistically significant. This means that patients with early prophylaxis at any point had their risk of VTE reduced almost by half.
  • All cause mortality. Could their be other issues with early VTE prophylaxis that would increase mortality? This analysis showed that the odds ratio was 0.83 favoring early prophylaxis decreasing it. This is a 17% reduction in mortality, but unfortunately was not statistically significant. Although there is a trend toward lower mortality with early prophylaxis, it is not significant.

Bottom line: Again, this type of analysis is powerful but can suffer from the combined weaknesses of its individual papers. However, the best information we have thus far shows that early prophylaxis prior to 72 hours of admission does not appear to be harmful, does not result in progression of intracranial bleeding or excess mortality, and cuts the risk of VTE almost in half.

In my next post, I’ll explore a recent paper that examines how early we can really go with VTE prophylaxis.

Reference: Clinical outcomes following early versus late pharmacologic thromboprophylaxis in patients with traumatic intracranial hemorrhage: a systematic review and meta-analysis. Neurological review 43:861-872, 2020.

Pharmacy

Unfractionated vs Low Molecular Weight Heparin For Trauma Patients

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In my last post, I described some of the telltale signs that could be seen in a trauma center’s TQIP report that might suggest there are issues with how they go about providing prophylaxis for venous thromboembolism for their patients. Today, I will analyze a systematic review and meta-analysis of a collection of research that compared the efficacy and safety of unfractionated heparin (UFH) to low molecular weight heparin (LMWH) specifically for trauma patients.

First, it’s important to understand the concept of research quality. There is a huge amount of research published these days, and it varies considerably in how well it is designed, executed, and analyzed. Here is a diagram that illustrates the levels of quality and the volume of research published at each level. By quality, I mean the applicability to clinical treatment of actual humans. For this reason, test tube and animal research are low on the pyramid.

The research that most people consider to be the “gold standard” (randomized, controlled, double blind) is very close to the top. There is one class that, if conducted properly, may even be better. That is the systematic review and meta-analysis.

Most people have heard of meta-analysis, and it can be very good by itself. This combines lots of smaller studies into one larger one. However, it may hampered by the quality of the studies included in the meta-analysis. The tenet of “garbage in equals garbage out” certainly holds. But a systematic review takes that one step further.

The systematic review compiles all possible studies related to a small set of research questions, and usually concentrates on the ones with the highest quality research design. The quality of each of the studies is evaluated, and a meta-analysis is then performed on the best. Results are usually represented in a forest plot. This is an easy way to illustrate the estimated results from a number of studies that address the same question. There is also an entry that shows the relative strength of all of the studies combined. Here’s an example:

There are seven studies included, and each is displayed with its risk ratio (RR) and confidence interval (CI). The final diamond is the combined RR and CI for the entire group of studies. In the example above, note that most of the studies have CI bars that extend over the risk ratio = 1 line, meaning they may not be significant. But when taken together, the final risk ratio of the group is well under 1.0 and does not cross over it, denoting significance.

Let’s now apply this concept to a group of studies comparing UFH and LMWH for prevention of VTE for trauma patients. Based on keyword search, the authors identified 1,227 records for screening. Of those, only 40 were tentativley found to directly address the question. After in-depth analysis, only 12 were eligible for final review. For various reasons, only about 1 in 100 papers could be used to try to analyze the question. This always shocks me.

Here are the efficacy results. All are statistically significant, and all but mortality were stated with moderate certainty. The mortality number had low certainty due to the fact there were only three studies and confidence intervals were very wide.

  • Deep venous thrombosis: LMWH reduced by about 35% compared to UH
  • Pulmonary embolism: LMWH reduced by 44% although certainty was low
  • Any VTE: LMWH reduced by about 30%
  • Mortality: LMWH reduced by 56% (low to very low certainty)

Safety was also analyzed, including bleeding events, unexpected return to OR, heparin induced thrombocytopenia (HIT), and “any adverse events.” All of the Total Confidence Interval diamonds were situated on the risk ratio = 1 line, denoting no significant change when comparing LMWH vs UH.  However, quality of this data was noted to be low due to the quality of the individual studies. This means that we do not really know the answer to the safety question with any certainty yet.

Bottom line: This is one of the best summaries of our research on UH vs LMHW to date. It broadly reviewed the available literature and found only a small subset to analyze. It is clear that LMWH is superior for prevention of DVT and VTE overall. However, the impact on pulmonary embolism and death is still unclear.

As far as safety, the studies are still of quality that is too low to use for a decent analysis. Although this study did not detect any increase in complications, we still can’t say with any degree of certainty.

So what does it all mean? We have been using LMWH for decades now. Most likely, if there were regular complications like bleeding, unexpected return to OR, or HIT we would have definitely noticed it by now. Fortunately, we only have a few anecdotes and case reports to scare us off.

Overall, there is good support for the use of LMWH exclusively in most trauma patients. However, the prescribing provider should always assess patient factors that may suggest that UH might be better is a specific case. But remember that using UH trades an unclear/unlikely safety advantage for a recognized decrease in efficacy.

Reference: Efficacy and safety of low molecular weight heparin versus unfractionated heparin for prevention of venous thromboembolism in trauma patients. Ann Surgery 275(1):19-28, 2022.