Category Archives: Pharmacy

ACS Trauma Abstracts #4: Timing Of DVT Prophylaxis In Spine Trauma

Spine trauma is one of the high-risk indicators for deep venous thrombosis (DVT). Unfortunately, there is a great deal of variability in the start time for chemical prophylaxis for this injury, especially after the patient has undergone surgery. In part, this is due to a lack of good literature and guidelines, and in part due to the preferences of the spine surgeons who operate  on these patients.

A group at the University of Arizona in Tucson performed a large database review (looks like National Trauma Databank, although they don’t say in the abstract) looking at “early” vs “late” administration of prophylaxis after surgery in these patients. The spine injury was the predominant one, with all other systems having an abbreviated injury score (AIS) < 3. They matched two years worth of patients for demographics, initial vitals, type of operative intervention, and type of heparin to assess the impact of prophylaxis timing.

Here are the factoids:

  • Nearly 40,000 patient records were reviewed, and over 9,500 met the spine injury criteria with operation and prophylaxis. A total of 3,556 could be matched for analysis.
  • These patients were split in half for matching, late (>48 hrs) versus early (<48 hrs)
  • DVT rate was significantly lowe in the early prophylaxis group (2% vs 11%)
  • PE rate and mortality were the same between groups
  • Return to OR and blood transfusion rates were identical (1% and 1-2 units)

Bottom line: Once again, we see that “early” prophylaxis for DVT is probably desirable and mostly harmless, even after a spine operation. Many surgeons still have an irrational fear of giving heparin products in patients who have some risk of bleeding. The body of literature that supports early use just keeps growing. One observation, though: as in most other studies, pretty much whatever we do for DVT has a negligible impact on PE and mortality. We can only treat the clots, but not their major aftermath.

Reference:  Optimal timing of initiation of thromboprophylaxis in spinal trauma after operative intervention: – propensity-matched analysis. JACS 225(4S1):S59-S69, 2017.

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Anticoagulants And The Elderly: Are They Being Appropriately Treated?

About 2.3 million people, or a bit less than 1% of the US population, have atrial fibrillation. This condition is commonly managed with anticoagulants to reduce the risk of stroke. Unfortunately, the elderly represent a large subset of those with a-fib. And the older we get, the more likely we are to fall. About half of those over 80 will fall once a year.

Are all of these elderly patients being treated with anticoagulants appropriately? Several scoring systems have been developed that allow us to predict the likelihood of ischemic stroke. Looking at it another way, they allow us to judge the appropriateness of using an anticoagulant to prevent such an event.

The original CHADS2 score was developed using retrospective Medicare data in the US. The newer CHA2DS2-VASC score used prospective data from multiple countries. However, the accuracy is about the same as the original CHADS2 score. But because the newer system has three more variables, it adds a few more people to the high-risk group who should receive an anticoagulant.

The higher the CHA2DS2-VASC score, the more likely one is to have an ischemic stroke. The threshold to justify anticoagulation seems to vary a bit, with some saying >1 and others going with >2. Here’s a chart that shows how the stroke risk increases.

Stroke risk per year with CHA2DS2-VASC score

Whereas CHA2DS2-VASC predicts the risk of clotting (ischemic stroke), the HAS-BLED score looks at the risk of bleeding. It includes clinical conditions, labile INR, and concomitant use of NSAIDs, aspirin or alcohol, but not a history of falls.

Proper management of atrial fibrillation in the elderly must carefully balance both of these risks to reduce potential harm as much as possible. A HAS-BLED score of >3 indicates a need to clinically review the risk-benefit ratio of anticoagulation. It does not provide an absolute threshold to stop it.

A group at Henry Ford Hospital in Detroit, a Level I trauma center, retrospectively reviewed their experience with patients who fell while taking an anticoagulant for atrial fibrillation. They calculated CHA2DS2-VASC and HAS-BLED for each and evaluated the appropriateness of their anticoagulation regimen.

Here are the factoids:

  • A total of 242 patients were reviewed, and the average age was 78
  • The average CHA2DS2-VASC score was 5, and the average HAS-BLED was 3
  • Only 1.6% were considered to be receiving an anticoagulant inappropriately (CHA2DS2-VASC 0 or 1)
  • Nearly 9% of patients were dead 30 days after the fall

Bottom line: The authors found that their population was appropriately anticoagulated. But they also noted that the morbidity and mortality risk was high, and was independent of age and comorbidities.

There are tools available to help us judge whether an elderly patient should be taking an anticoagulant for atrial fibrillation. The tool for predicting bleeding risk, however, is not as good for trauma patients. It ignores the added risk from falling, which is very common in the elderly.

Every patient admitted to the trauma service after a fall should have a critical assessment of their need for anticoagulation. The specific drug they are taking (reversible vs irreversible) should also be examined. If there is any question regarding appropriateness, the primary care provider should be contacted personally to discuss and modify their drug regimen. Don’t just rely on them reading the hospital discharge summary. Falls can be and are frequently fatal, just not immediately. Inappropriate use of anticoagulants can certainly contribute to this problem, so do your part to reduce that risk.

Related links and posts:

Reference: Falls, anticoagulation, and the elderly: are we inappropriately treating atrial fibrillation in this high-risk population? JACS 225(4S1):S53-S54, 2017.

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Is Fine-Tuning Lovenox Dosage Using Anti-Factor Xa Worthwhile?

Deep venous thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE), are major concerns in all hospitalized patients. A whole infrastructure has been developed to stratify risk, monitor for the presence of, and provide prophylactic and/or therapeutic drugs for treatment. But if you critically look at the literature from the past 20 years or so, we have not made much progress.

One of the newer additions to our arsenal has been to figure a way to determine the “optimal” dose of enoxaparin. Three options are now available: weight-based dosing, confirmation by thormboelastography (TEG), and anti-factor Xa assay. Let’s look at another paper that focuses on the last item.

Anti-factor Xa levels provide a way to monitor low molecular weight heparin activity. A number of papers published have sought to determine a level that predicts adequate activity. Although they are not of the greatest size or quality, a range of 0.2-0.4 IU/ml seems to be the consensus.

A large number of patients at a busy Level I trauma center were retrospectively studied to see if achieving a peak anti-factor Xa level of at least 0.2 IU/ml would result in less VTE. All patients were started on enoxaparin 30mg SQ bid within 48 hours of admission. Anti-factor Xa was measured 4 hours after the third dose. If the level was less than 0.2 IU/ml, the dose was increased by 10mg per dose. The cycle was repeated until anti-factor Xa was therapeutic.

Here are the factoids:

  •  All patients with a Greenfield Risk Assessment Profile (RAP) of 10 or more (high risk) were included; duplex ultrasound surveillance for lower extremity DVT was performed weekly
  • 194 patients were included, with an average RAP of 9 and ISS of 23 (hurt!)
  • Overall VTE rate was 7.4%, with 10 DVT and 5 PE (!)
  • Median time to diagnosis was 14 days
  • Initial anti-factor Xa levels were therapeutic in only one third of patients, and another 20% reached it after dose increases. 47% never achieved the desired level, even on 60mg bid dosing.
  • There was no difference in DVT, PE, or VTE rates in patients who did vs did not achieve the goal anti-factor Xa level
  • Injury severity and obesity correlated with inability to reach the desired anti-factor Xa level

Bottom line: In this study, achieving or not achieving the goal anti-factor Xa level made no difference whether the patient developed VTE or not. And it was difficult to achieve anyway; only about half ever made it to the desired level. How can this happen?

Well, there are still many things we don’t understand about the genesis of VTE. There are probably genetic factors in every patient that modify their propensity to develop it after trauma. And there are certainly additional mechanisms at play which we do not yet understand. 

For now, we will continue to struggle, adhering to our existing protocols until we can figure out the real reason(s) VTE happens, the best ways to prevent, and the best methods to treat.

Related posts:

Reference: Relation of Antifactor-Xa peak levels and venous thromboembolism after trauma. J Trauma accepted for publication Aug 2, 2017.

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Aspirin For DVT Prophylaxis In Trauma

The use of mechanical and pharmacologic prophylaxis for prevention of deep venous thrombosis (DVT) and venous thromboembolism (VTE) in trauma patients is nearly universal. However, no matter how closely we adhere to existing guidelines, some patients will develop these conditions. Indeed, about 80% of patient who suffer some type of VTE event were receiving prophylaxis at the time.

Trauma is a major factor in causing hypercoagulability. Although current chemoprophylaxis focuses on clotting factors, platelets play a big part in the clot formation process. Our usual drugs, though (various flavors of heparin), have no effect on them.

What about adding aspirin to the regimen? My orthopedic colleagues have been requesting this for years. There is a reasonable amount of data in their literature that it is effect in patients with knee arthroplasty only. As usual, it is misguided to try to generalize management based on experience from one specific body region or operation.

A single Level I trauma center reviewed its data on aspirin prophylaxis for trauma patients. They reviewed their registry data from 2006 to 2011. They identified 172 trauma patients with duplex ultrasound proven DVT. These patients were matched with 1,901 control patients who underwent at least one duplex and never developed DVT. Matching was performed carefully to ensure that age, probability of death, number of DVT risk factors, and presence of TBI were similar. The total number of matched patients studied was 110.

And here are the factoids:

  • About 7% of patients with DVT were on aspirin at the time of their injury, vs 14% of the matched controls
  • 7% were taking warfarin, and 4% were taking clopidogrel
  • Analysis showed that patients taking aspirin had a significantly decreased chance of DVT after injury
  • On further analysis, it was found that this effect was only significant if some form of heparin was given for prophylaxis as well.

Bottom line: So before you run off and start giving your patients aspirin, think about what this study really said. Patients taking aspirin before their injury and coupled with heparin after their injury have a lower rate of DVT. It gives us no guidance as to whether adding aspirin after the fact, or using aspirin alone, are useful.  And we still don’t know if any of this decreases pulmonary embolism or mortality rates.

Related posts:

Reference: Aspirin as added prophylaxis for deep vein thrombosis in trauma: a retrospective case-control study. J Trauma 80(4):625-30, 2016.

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Treating Headache After TBI

Most patients with mild traumatic brain injury (TBI) recover quickly and have few sequelae. Headache is common during the first few hours or days. But some patients experience significant and sometimes unrelenting headaches after their injury. How should we treat them? Are they the same as other common headaches?

There are several common types of headaches that are not related to brain injury, but many of these can begin after TBI. These include tension headaches from muscle tension or spasm, cervicogenic headaches from strains, sprains or more significant injury to the neck and cervical spine, musculoskeletal headaches from pain in bone or muscle in the head or neck, and headaches related to the TMJ and jaw.

But many patients experience significant headaches without any of these factors. Why? Sometimes it is due to blood in or around the brain, irritating the meninges. But often, there is nothing that we can detect using our current diagnostic technology. However, even if we can’t find a reason, the headache is very real and very concerning to the patient.

I’ve seen practitioners treat post-TBI headaches with a variety of drugs ranging from acetominophen and NSAIDs to anti-seizure and psychotropic drugs. Unfortunately, there is little literature support for any of them. A review article published in 2012 found only one article with Class II data that showed no lasting effect from manipulation therapy.

So what do we do? Here is an algorithm suggested by the review article:

  • Consider a workup to rule out intracranial pathology as a source of the headache
  • Categorize the headache. If it is one of the non-TBI types listed above, treat appropriately.
  • If the headache severely limits function, consider time-release opioids
  • For milder headache, consider adetominophen or NSAIDs
  • Treat any comorbidities that may contribute to headache
  • If the headache has migraine-type properties, treat as such
  • If the headache is associated with cervical spine pain, mobilize the neck as appropriate

Bottom line: There is very little guidance for treatment of headache purely associated with TBI. Time-honored drugs like opioids for severe pain and acetominophen and NSAIDs for mild to moderate pain help, but generally do not entirely relieve the pain. Only tincture of time will make things better. And it’s probably best to stay away from prescription drugs other than opioids recommended for the pain. They have not been shown to work, and there are plenty of side effects to worry about.

Related post:

  • Prescription drugs and side effects

Reference: Systematic review of interventions for post-traumatic headache. PM&R. 4(2):129-140, 2012.

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