Category Archives: Head

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.

Print Friendly, PDF & Email

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!

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

Print Friendly, PDF & Email

Best Of EAST #15: Prehospital TXA

The world is divided into trauma centers that are TXA believers and those that are TXA nonbelievers. It all depends on how one interprets the CRASH-2 data and subsequent studies. Then came CRASH-3 with TXA use for patients with TBI. This large study found improved survival in patients with mild to moderate head injury when given “early.”

The group at Oregon Health Science University tried to better define this concept of “early.” They examined early vs later administration of TXA in patients with moderate to severe TBI. Note that this degree of head injury is a bit different than CRASH-3 (mild to moderate in CRASH-3 and moderate to severe in this one). This was a multicenter trial that included patients with GCS < 12 and who were hypotensive with SBP < 90. Patients received either a 1g bolus followed by a 1g infusion over 8 hours, or a 2 g bolus only. The authors subdivided these patients into early administration (<45 minutes after injury) or late (45 minutes to 2 hours after injury).

Here are the factoids:

  • There were 354 patients in the early administration group and 259 in the late group
  • All outcomes, including 1 month and 6 month mortality and the extended Glasgow outcome scale were not significantly different between early and late groups (exact numbers were not given)
  • There was no difference in secondary complications between the groups (again, exact numbers or complication types were not given)

The authors concluded that there was no difference in outcomes in early vs later administration of TXA in these head injured patients. They suggest that patients can be given TXA anytime within two hours without loss of benefit.

Bottom line: Essentially, this ends up as a noninferiority study. The biggest question with this type of study is, do you have enough subjects to detect a significant difference? Taken to an extreme, let’s say you have 5 patients who receive a drug who are compared to 5 who did not for some mystery condition. Three who did not get the drug die (60% mortality), but only two who get it do (40% mortality). In relative terms, there was 33% decrease in mortality with the drug. But in absolute terms, it was one patient. Would anyone see this as a significant result with such small numbers?

But now multiply by a thousand, and 300 die without the drug and only 200 die who were given it. The relative difference is the same, but the absolute difference is beginning to look large and significant.

So the smaller study won’t meet the test of significance but the larger one will. The key question in the TXA study here is, do they have enough patients enrolled to show there is no real difference between the groups? I love doing back of the napkin power analyses, and I admit I certainly don’t have all the numbers and probabilities needed for a precise calculation. But the groups sizes in this study (354 vs 259) seem a bit small to achieve significance unless there are large disparities in outcomes. 

I certainly recognize that it’s just not possible to put all the relevant information for a research project into a four paragraph abstract. One would need to be able to submit 12 slide PowerPoint decks. So I’m sure more info will be available as I take in the presentation next Friday.

Here are my questions for the authors and presenter:

  • The study is nicely designed as a randomized, double-blind trial, but how did you blind one vs two doses? Did everyone get an infusion of something, TXA vs saline?
  • Why did you select 45 minutes as the cutoff for early vs late administration? Was this arbitrary or is it based some data?
  • Show us the power analysis that demonstrates the total number of patients in the study is sufficient to show us true non-significance in your results.
  • And I’m sure you will show the actual survival and complications numbers (and type) in the presentation, since they were not available in the abstract.

Reference: THE EFFECTS OF TIMING OF PREHOSPITAL TRANEXAMIC ACID ON OUTCOMES AFTER TRAUMATIC BRAIN INJURY. EAST 35th ASA, oral abstract #40.

Print Friendly, PDF & Email

Best Of EAST #10: (F)utility Of ICP Monitoring In Geriatric Patients?

Patients with severe TBI are typically managed using staged protocols based on the Brain Trauma Foundation (BTF) guidelines for ICP monitoring. There have been a number of papers over the past six years that question the utility of ICP monitoring, at least using the procedures in the BTF guidelines.  Most of these studies do not specifically break out elderly patients.

The group at the Westchester Medical Center in NY used the TQIP database to review the impact of ICP monitoring for severe TBI in patients > 65 years old. They performed a four year database study on these patients with an isolated head injury (no other body regions with AIS > 2), initial GCS < 8, and a length of stay > 24 hours. The examined the presence or absence of an ICP monitor, AIS head score, GCS, and a number of outcome measures.

Here are the factoids:

  • A total of 4,433 patients met the above criteria, and 17% had an ICP monitor placed
  • After propensity matching for those with and without an ICP monitor, mortality was nearly identical in both groups at 49%
  • ICU length of stay, hospital length of stay, and ventilator days were significantly longer in the monitor group

The authors concluded that ICP monitoring in this elderly group of patients did not improve survival and increased length of time in the ICU, hospital, and on the ventilator. The recommend that the current guidelines be improved to recognize these facts.

Bottom line: This is a nice, simple study that sought to answer just a few nice, simple questions. The mortality results are convincingly equal between the groups with and without an ICP monitor. The lengths of stay and ventilator days are statistically significantly longer with p values < 0.001. However, the actual numbers are not provided. I have seen many studies where statistically different numbers are not clinically relevant.

There are a number of papers that have come to similar conclusion on other or broader groups of TBI patients. Although we have specific guidelines on who gets a monitor and what we do with the numbers, there is growing doubt that their use actually helps. Perhaps it is time for us to review the data and make appropriate revisions!

Here are my questions for the authors and presenter:

  • Tell us about your propensity score matching. This will help us understand how similar the patient groups really were, with the exception of their ICP monitors.
  • Please provide the actual numbers for your lengths of stay and ventilator days. We need to be sure these are clinically and/or financially significant.
  • Have the results of this work prompted you to rework your own practice guidelines for treatment of severe TBI? I’m always interested if the group feels strongly enough about their work that they would consider changing their practice based on it.

Reference: ROLE OF ICP MONITORING IN GERIATRIC TRAUMA PATIENTS. EAST 35th ASA, oral abstract #33.

 

Print Friendly, PDF & Email

Best Of EAST #9: Routine Repeat Head CT For TBI Patients On Antithrombotic Agents

The data we use as guidance for repeat head CT in elderly patients who sustain mild TBI while taking antithrombotic therapy remains limited. There is a slowly growing consensus that the need is limited, but there is still a very wide variation in practice patterns.

The group at HCA Healthcare Nashville collected data from 24 system hospitals on this very specific cohort of patients: elderly (age > 55), head trauma with GCS 14-15, an initial head CT, and no other injuries with AIS > 2. They divided these patients into two groups based on whether they were currently taking antithrombotic (AT) therapy. Rate of delayed intracranial hemorrhage (ICH), need for neurosurgical intervention, and mortality were compared.

Here are the factoids:

  • About 3,000 patients were enrolled and only 10% had a repeat head CT
  • Of those who were rescanned, 10% of patients on meds had a new ICH vs 6% in those not taking meds (not statistically significant)
  • Extrapolating those numbers to all patients, the rate of delayed ICH would be 0.7% in patients not taking AT vs 1.0% for those who were (also not significant)
  • Mortality attributable to a head bleed occurred in only one patient who was made comfort care
  • There were no neurosurgical procedures performed in either group

The authors concluded that this specific subset of patients has a very low rate of delayed ICH, and that there are minimal clinical consequences in those that do. They do not support repeat head CT.

Bottom line: This abstract adds to the growing body of literature that shows little benefit to repeat head CT scan after a negative initial study, even if the patient is on blood thinners. Many previous studies involve only a single center and/or have smaller numbers. This one is larger because of the size of the HCA trauma system, and answers a simple set of questions on a limited subgroup of patients: elderly, mild TBI, with limited other injuries.

My back of the envelope power calculations show the authors may be a little short of the number of subjects to be able to show that the difference in the number of delayed ICH (0.7% vs 1.0%) is statistically significant. But the numbers are close enough and the p value so large (0.3) that they are probably right. This is completely offset by the absence of necessary neurosurgical interventions and the single attributable death.

Many trauma centers, including my own, have adopted a “no repeat scan” policy after a negative initial scan, even on thinners. In fact, unless the patient has some other injury that requires admission, they are discharged home with a responsible adult.

Here are my questions for the authors and presenter:

  • Did you do any type of power analysis to determine if the large number of patients included was actually large enough?
  • The term “antithrombotic therapy” is used broadly; which agents were considered in this category? Traditional warfarin therapy? Aspirin and other antiplatelet agents? DOACS?
  • Have you changed your system guidelines to reflect your work?

This is important and practical work! I’m looking forward to hearing all the details.

Reference: ROUTINE REPEAT BRAIN CT SCANNING IS UNNECESSARY IN OLDER PATIENTS WITH GCS 14-15 AND A NORMAL INITIAL BRAIN CT SCAN REGARDLESS OF PREINJURY ANTITHROMBOTIC USE: A MULTICENTER STUDY OF 3033 PATIENTS. EAST 35th ASA, oral abstract #31.

Print Friendly, PDF & Email