Tag Archives: Prophylaxis

Abstracts, Pharmacy

Best Of AAST #5: Door-To-Prophylaxis Time

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Today’s abstract continues the theme of VTE prophylaxis. The authors introduce another timing parameter in this one: the “door-to-prophylaxis” time. Just as it sounds, this is the time interval between admission to the ED and initiating chemo-prophylaxis. Just like some centers struggle with how long to wait to start it after a solid organ injury (see previous post here), many find it challenging to get it ordered in the first place.

The authors retrospectively reviewed their registry data over four years. They compared adult patients who arrived as a highest-level of activation and received blood during their resuscitation. They were divided into two groups: those with DVT or pulmonary embolism (VTE group) and those without (no VTE group). The door-to-prophylaxis time was defined as the time from hospital arrival to the first dose of medication.

Here are the factoids:

  • Just over 2,000 patients met inclusion criteria, with 106 experiencing VTE and 1,941 without it
  • VTE patients had higher ISS (29 vs. 24), higher lactate levels (4.6 vs. 3.9), and more post-ED blood transfusions (8 vs. 2)
  • There was no difference in the need for dose adjustment or missed doses between the groups
  • Door-to-prophylaxis time was significantly longer in the VTE group (35 vs. 25 hours)
  • When controlling for age, sex, ISS, lactate, and post-ED transfusions, each hour of delay increased the likelihood of VTE by 1.5%

The authors concluded that the door-to-prophylaxis time was significantly associated with increased incidence of VTE. They suggest that the door-to-prophylaxis time should be utilized as a performance improvement metric for this condition.

Bottom line: Unfortunately, we need a lot more information here. There was not enough room for details about the statistical analysis in the abstract, but they will be essential to know. And the authors remind us that this study shows association, not causation. 

Severe injury and blood transfusion are already known to be associated with a higher likelihood of VTE. The fact that the longer door-to-prophylaxis group had more frequent VTE may very well be due to their higher ISS and greater number of transfusions. Those events themselves may have led to the hesitation in starting a heparin.

Early prophylaxis is certainly a desirable goal in any trauma patient. But we need more than a new metric. We need more concrete information on the specific reasons for the delay and to prove that it is safe to give the drug early in patients who have those potential delaying factors.

Reference: “Door-to-prophylaxis” time as a novel quality improvement metric in preventing venous thromboembolism following traumatic injury. AAST 2023, Plenary paper #38.

Abdomen, Abstracts, Pharmacy

Best Of AAST #4: Starting VTE Prophylaxis After Solid Organ Injury

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Venous thromboembolic disease (VTE) continues to be a major issue in trauma patients. Most trauma centers have prophylaxis guidelines to try to reduce this problem. These guidelines typically recognize specific injuries that increase the risk of bleeding if anticoagulants are given. Typical ones include hemorrhagic injuries to the brain, pelvic and spine fractures, and solid organ injuries.

Typically, VTE prophylaxis starts immediately upon admission. But when these high-risk injuries are present, it is usually delayed for a period of time. Unfortunately, that period may be highly variable. Many centers have adopted 2-3 days to delay administration of low molecular weight heparin in patients with solid organ injury.

The AAST initiated a prospective multi-institutional trial comparing early (<48 hours after admission) and late (>48 hours) administration of prophylactic agents. Patients were older than 16 years, had any number of liver, spleen, or kidney injuries, and were initially treated nonoperatively. Patients who were transferred, died in the ED, were pregnant, had a bleeding disorder, or were taking anticoagulants or platelet inhibitors were excluded. A power analysis was performed, and more than the needed number of patients were enrolled.

Here are the factoids:

  • A total of 1173 patients were enrolled, and there were 589 liver injuries, 569 spleen injuries, and 289 kidney injuries
  • About 75% of patients (864) had early prophylaxis
  • Patients were younger (median 34 years), and two-thirds were male, with a median ISS of 22
  • Early VTE prophylaxis patients had significantly lower rates of VTE (3% vs. 7%)
  • There was no significant difference in failure of nonoperative management (5% early vs. 7% late)
  • The early prophylaxis group received fewer units of blood after prophylaxis started (17% vs. 23%)
  • Patients receiving VTE prophylaxis after 48 hours were 2.2x more likely to develop VTE

The authors concluded that early VTE chemoprophylaxis was associated with lower rates of VTE with no increase in complications. They recommended that it should become the standard of care for these patients.

Bottom line: Seeing such a well-designed and nicely executed study is refreshing. If the facts are borne out in the final manuscript review, this should become the standard of care for VTE prophylaxis in patients with solid organ injuries. 

I wish the authors would have stipulated that the chemoprophylaxis was required to be low molecular weight heparin. Unfortunately, there are still more than a few centers using unfractionated heparin. There could be a difference in efficacy and failure rates between the two. This could complicate the statistical analysis. Hopefully, the presenter will address this during the meeting.

I would also like to see a breakdown of when the early VTE prophylaxis actually started. Were they all close to 48 hours? Or were there enough at 24 hours to show this is also safe and effective?

It’s time for everyone to review their VTE prophylaxis guidelines. Get ready to make some major changes in your patients with solid organ injury!

Reference: When is it safe to start VTE prophylaxis after blunt solid organ injury? A prospective AAST multi-institutional trial. AAST 2023, Plenary paper #23.

Abstracts, Complications, Head

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

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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.

Abstracts, Pharmacy, Solid organ

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

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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.

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.