Category Archives: Pharmacy

Opioids In Trauma Care: Food For Thought

Here’s something I ran across during my reading last week. In the “old days”, I used to encourage my trainees to be generous with pain medicine prescriptions for patients being discharged from the hospital. I would routinely send people home with 60, 75, or more pills. I got a hint of the folly of this just a few years ago when I underwent an outpatient procedure (biceps tendon repair).

The orthopedic surgeon prescribed 15 narcotic pain pills for me to take home. I scoffed at the low number, although I didn’t tell him that. But once I got home and the regional block wore off, how many do you think I took? Exactly one. I (safely) disposed of the rest. This prompted me to start rethinking our role in the opioid problem here in the US.

Tomorrow, I’ll write about a recently published paper and guideline for discharge opioid prescriptions. But today, watch the TED talk embedded below. It reveals the inadequacies within our health care system for those who, one way or another, have developed a dependence on these medications. It was an eye-opener for me.

DVT Prophylaxis At Home: Do Our Patients Do What They Are Told?

Deep venous thrombosis (DVT) is a big potential problem for many trauma patients, particularly those with orthopedic injuries. Patients at high risk are frequently given a prophylaxis regimen to take home after discharge while they are still at higher risk for clots. The particular choice of medication typically comes down to oral (warfarin or aspirin) vs injectable (low molecular weight heparin (LMWH)).

There is quite a bit of literature on patient compliance with their medication routines, or should I say noncompliance? The group at ShockTrauma in Baltimore evaluated how well orthopedic surgery patients adhered to their prescribed DVT prophylaxis schedule after discharge.

They conducted a randomized, prospective trial on all patients who underwent operative management of extremity or pelvic fractures. These patients were prescribed either oral low dose aspirin (81mg) or subcutaneous injections of LMWH (30mg bid). All completed a standardized 8-question tool to gauge their compliance with the medication regimen. Nicely, a power analysis was performed to identify the minimum number of patients needed to achieve statistical significance ( 126 total patients).

Here are the factoids:

  • Of 1450 potential patients undergoing operative fracture fixation, 329 were eligible for the study. All but 150 were excluded primarily due to no need for prophylaxis or inability to contact.
  • Overall adherence to the prophylaxis plan was fairly high, with 65% of patients having high adherence, 21% medium, and 20% low.
  • A quarter of the LMWH patients felt “hassled” by their regimen, while only 9% of the aspirin group did
  • LMWH prophylaxis was associated with low or medium adherence
  • Having to self-administer the prophylactic agent, being a male, and young was also associated with lower compliance

Bottom line: Interesting study. And unfortunately it suggests that our patients don’t always do what they are told, especially if they have to stick themselves with needles. So they may not be getting the prophylaxis we think they are. Furthermore, we’re not even sure if aspirin (or LMWH for that matter) make a difference in the incidence of death or major pulmonary embolism in these patients.

There are a lot of opportunities for mayhem in this study. A third of the enrolled patients were not even compliant with completing the survey. This is certainly a source of bias, and most likely suggests that the overall compliance rates would have been even lower if they had. 

Keep in mind the risk factors for compliance (age, sex, drug route) when deciding how and what to provide for DVT prophylaxis. Your patient may not be doing what you assume they are!

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.

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.

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.