Category Archives: Pharmacy

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

August 11, 2017 The Trauma Pro Leave a comment

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.

Complications, General, Pharmacy

Aspirin For DVT Prophylaxis In Trauma

May 2, 2017 The Trauma Pro Leave a comment

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.

Pharmacy

Treating Headache After TBI

March 1, 2017 The Trauma Pro Leave a comment

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.

Pharmacy

How Many Salt Tabs In A Liter Of Saline?

December 14, 2016 The Trauma Pro Leave a comment

Seems like a simple, silly question, right? I dare you to figure it out without reading this post!

horse-salt-block-lick2

On occasion, our brain injured trauma patients have sodium issues. You know, cerebral salt wasting. Trying to maintain or regain the normal range, without making any sudden moves can be challenging. There are a lot of tools available to the trauma professional, including:

Saline
Hypertonic saline
Salt tablets
Fluid restriction
Some combination thereof

Fun times are had trying to figure out how much extra sodium we are giving with any of the first three items. This is important as you begin to transition from the big guns (hypertonic), to regular saline, and then to oral salt tabs.

Below is a quick and dirty conversion list. I won’t make your heads explode by trying to explain the math involved changing between meq, mg, moles, sodium and sodium chloride.

The “normal saline” bags we use are actually 0.9% saline (9 gm NaCl per liter)
Hypertonic saline can be 3% or 5% (30 gm or 50 gm per liter)
Salt tabs are usually 1 gm each (and oh so yummy)

Therefore, a liter of 0.9% normal saline is the same as 9 salt tabs.

A liter of 3% hypertonic saline is the same as 30 salt tabs. The usual 500cc bag contains 15.

A liter of 5% hypertonic saline is the same as 50 salt tabs. The usual 500cc bag contains 30.

To figure out how many tablets you need to give to match their IV input, calculate the number of liters infused, then do the math! And have fun!

Pharmacy

Battle of the Heparins: Unfractionated vs Low Molecular Weight

August 25, 2016 The Trauma Pro Leave a comment

Most trauma programs tend toward using low molecular weight heparin (LMWH) products for VTE prophylaxis over plain, old-fashioned unfractionated heparin (UH). How did this happen? LMWH is more expensive than UH, and there is precious little high quality research supporting it.

But, LMWH is very convenient, as it only needs to be given only once or twice daily via subq injection, whereas UH is given as a continuous infusion or subq three times a day. And a fair amount of lower quality data suggests that it is effective in decreasing deep venous thrombosis (DVT) and pulmonary embolism (PE).

This abstract comes from Sunnybrook in Toronto. The authors used sophisticated statistical models to compare centers that predominantly use LMWH to prevent VTE vs those that use UH.

Here are the factoids:

This was a huge data analysis from the ACS Trauma Quality Improvement Program database (~ 110,000 records from 214 trauma centers)
LMWH was most commonly used, 74% of the time
Patients who were more likely to need rapid reversal were more often given UH (older patients, severe TBI, early intracranial interventions)
Pulmonary embolism was significantly lower with LMWH (1.8% vs 2.4%)
This significant effect was present across all subgroups, including patients with shock, blunt multisystem injury, penetrating trunk injury, isolated orthopedic injury, and severe TBI
Trauma centers that predominantly used LMWH had significantly lower PE rates compared to UH (1.2% vs 1.8%)

Bottom line: Even given the vagaries of using huge, retrospective database reviews, this is pretty good data. The use of LMWH appears to be superior to UH in reducing the incidence of pulmonary embolism. It does not prevent it completely. But it’s a good start.

What the authors do not say, and I am curious about, is the impact on DVT. That is a much more common problem than PE. Was there any difference? Did they run out of room to comment on it in the abstract? I kind of doubt it. The devil will be in the details. Listen in on the presentation at the meeting!

Reference: Efficacy of low molecular weight heparin vs unfractionated heparin to prevent pulmonary embolism following major trauma: results from the American College of Surgeons Trauma Quality Improvement Program. AAST 2016 Paper #5.

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