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.

Source: The Trauma Professionals’s Blog

By Request: Drugs Are Chemicals??

This is another one of my most popular posts. Many patients (and more than a few doctors) have a hard time grasping the fact that the medications that we prescribe often do more than just one thing. They actually do many, many things most of the time. Sometimes too many. Here’s the post:

One of the cornerstones of allopathic medicine is the use of drugs to treat disease conditions. And unfortunately, one of the side effects of using drugs to treat problems is the production of side effects(!).

In trauma care, even something as simple as treating pain from an injury can create major problems. Give a narcotic pain medication. The patient gets nauseated and vomits. Try a different narcotic. The patient develops constipation. Give stool softeners and cathartics. Diarrhea. Then pseudo-obstruction develops. Give neostigmine. The patient becomes bradycardic. Give… well, you get the picture.

How common are side effects? Very! Did anyone see the first TV commercials for Chantix, the smoking cessation drug? It was about 3 minutes long because of the long list of side effects that were described. I’m surprised anyone was willing to risk them just to stop smoking cigarettes.

A recent study looked at the number of side effects listed on the labels of 5,602 medications approved by the FDA. There were a grand total of 534,125 adverse drug effects described in the packaging. Some interesting statistics:

  • The number of adverse effects for ranged from 0 to 525(!) for a single drug
  • The median number of adverse effects was 49, the average was 70
  • Drugs with the most side effects are used in neurology, psychiatry and rheumatology
  • Newer drugs had significantly more adverse effects than older ones

It’s certainly easy to bash pharmaceutical companies on their products. But some of these findings may be due to more rigorous testing and monitoring, as well as nuances in the populations in which these drugs are used.

Bottom line: Drugs are chemicals! Each chemical has a number of effects, some of which are desirable, and some of which are not. The drug companies choose to market a drug based on one desired effect (e.g. control of nausea). Just remember, when you give that medication, you will probably get the desired effect, but you will just as likely also get some of the other 69 possible side effects. Be prepared, and prescribe sensibly.

Reference: A quantitative analysis of adverse events and “overwarning” in drug labeling. Arch Int Med 171(10):944-946, 2011.

Source: The Trauma Professionals’s Blog

Could Be A Urethral Injury, But The Catheter’s Already In?

You’re seeing a trauma patient, probably a transfer from somewhere else. Either they told you there “may have been” some blood at the tip of the urethra, or maybe you see it smearing the outside of a urinary catheter that’s already in place! How do you proceed from here?

First, try not to get into that situation. Make sure that everyone on your team knows that gross blood at the meatus, male or female, means urethral injury until proven otherwise. If it’s not gross blood, it could be that the patient was incontinent and has hematuria from other causes. The fear with passing a catheter across a urethral injury is that it may convert a partial tear to a complete one. Reconstruction and complications from the latter are far more serious.

But the catheter is there. What to do?

First, leave the catheter in place. You must assume that the injury is present, and you need to rule it in or rule it out in order to decide what to do with the catheter. If the injury is not really there, then you can remove the catheter when indicated. If it really is present, then the urethral injury is being treated appropriately.

Next, do a urethrogram. I’ve previously described how to do it here, but the technique I describe is only appropriate for uncatheterized patients. The technique must be modified to use thin contrast and a method to inject alongside the catheter. To do this, fill a 20-30cc syringe with contrast (Ultravist or similar liquid) and put an 18 gauge IV catheter on the tip (no needles, please). Slide the IV catheter alongside the urinary catheter, clamp the meatus with your fingers, pull the penis to the side and inject under fluoroscopy. The contrast column will not be as vivid as with a regular urethrogram because it is outlining the urinary catheter, so there is less volume.

If the contrast travels the length of the urethra and enters the bladder without leaking out into soft tissue, there is no injury. If there is contrast leakage, stop injecting and plan to call a urologist.

Finally, be on the lookout for associated injuries. Urethral injuries are frequently found in patients with anterior pelvic fractures and perineal injuries.

Related post:

Link: blood at the urethral meatus (Atlas-Emerg-Medicine.org.ua from McGraw-Hill)

Source: The Trauma Professionals’s Blog

Thoughts On Traumatic Hematuria: Part 2

Yesterday, I discussed blood in the urine from a urethra. As I mentioned, there is typically not much from that particular injury. Today, I’ll dig into the three causes of real hematuria.

All of these tubes show gross hematuria except the one on the right.

  • Bladder injury. This can occur with either blunt or penetrating injury. The degree of hematuria is variable with stabs or gunshots, but tends to be much darker in blunt injury. This happens because the size of the bladder injury tends to be greater with blunt force. The bladder injury is not necessarily full-thickness with blunt trauma. It may just be some wall contusion and underlying mucosal injury. But frequently, with seat belt injury and/or A-P compression injuries to the pelvis (“open book”), the injury is full thickness.
    • Tip: If less than 50cc of very dark urine flow from the catheter upon insertion, it is likely that your patient has an intraperitoneal bladder rupture!
  • Ureteral injury. This injury is very rare. The most common mechanism is penetrating, but this structure is so small and deep that it seldom gets hit by naything. Patients with multiple lumbar transverse process fractures will occasionally have a small amount of hematuria, probably from a minor contusion. More often than not, the hematuria is microscopic, so we should never know about it.
  • Kidney injury. The most important fact regarding renal injury is that the degree of injury has no correlation with the amount of hematuria. The most devastating injury, a devascularized kidney, frequently has little if any gross hematuria. And conversely, a very minor contusion can produce very red urine.

So what about diagnosis? It’s easy! If you see gross hematuria, insert a foley catheter (if not already done) and order a CT of the abdomen/pelvis with contrast, as well as a CT cystogram. The latter must not be done using passive filling of the bladder with a clamped catheter. Contrast must be infused into the bladder under pressure to ensure a bladder injury can be identified.

CT scan is an excellent tool for defining injuries to kidney, ureter, and bladder, and will identify extravasation into specific places and allow grading. Specific management will be the topic of future posts.

Source: The Trauma Professionals’s Blog

Thoughts On Traumatic Hematuria: Part 1

I’ve seen a number of patients recently with bloody urine, and that is prompting me to provide some (written) clarity to others who need to manage this clinical problem. I’ll try to keep it organized!

There are two kinds of hematuria in trauma: blood that you can see with the naked eye, and…

Okay, so there’s only one. Trauma professionals do not care about microscopic hematuria. It does not change clinical management. Sure, your patient might have a renal contusion, but you won’t do anything about that. Or, he/she might have an infarcting kidney. And you can’t do anything about that. If you order a urinalysis, you might see a few RBCs. Don’t let this lead you down the path of looking for a source. You’ll end up ordering lots of tests and additional imaging, and generally will have nothing to show for it at the end. It’s not your job to spend good money on the very rare chance of finding something clinically significant.

Both of these specimens have blood in them. You can’t see it on the left, so don’t go looking for it with a microscope.

There are four sources of blood in the urine.

1. The first source does not generally cause hematuria, but can occasionally cause a few visible wisps of blood. That source is a urethral injury. The textbook teaching, and it’s good advice, is to look at the urethral meatus in your trauma patient, especially if you are contemplating insertion of a urinary catheter. If you see a few drops of blood, pause to consider. Sometimes, the blood is no longer visible, but might be present as a few well-placed drops on the patient’s underwear. So have a look at that, too, especially in patients with high risk injuries such as A-P compression pelvic fractures (think, lots of ramus fractures or pubic diastasis).

If you didn’t notice it and inserted the catheter anyway, you might see a few wisps of blood in the tubing as you place it. More often than not, this is just run of the mill irritation of the mucosa by the catheter, but always keep the possibility of an injury in mind.

Tomorrow, I’ll discuss the remaining three sources, and what to do about them.

Related posts:

Source: The Trauma Professionals’s Blog

The August Trauma MedEd Newsletter Is Coming Soon: The Laws of Trauma

I’m going to send out the next edition of the Trauma MedEd newsletter early next week. In this one, I’ll be presenting and discussing some of the “Laws of Trauma” that I’ve observed over the years. I think you’ll find them interesting and amusing.

As always, this issue will go to all of my subscribers first. If you are not yet one of them, click this link to sign up and/or download back issues.

Unfortunately, non-subscribers will have to wait until I release the issue on this blog, about 10 days later. So sign up now!

Source: The Trauma Professionals’s Blog

When Can You Take A Hypotensive Patient To CT?

The last two posts, I went on a rant about taking hypotensive patients to CT. The bottom line is that this is a generally bad idea, even if bad papers say it’s okay. However, we all know that there are no absolutes, especially in trauma.

So yes, there are two cases where one could justify taking a hypotensive patient to CT scan. Here they are:

  1. You believe that your patient has a catastrophic brain injury which is responsible for the hypotension. You would like CT confirmation so you can begin to withdraw support and terminate any other interventions.
  2. Your patient has sustained a cervical spinal cord injury and has neurogenic shock. You have started fluid resuscitation and are considering a pressor to normalize blood pressure, but would like to continue your diagnostic routine.

But before you can even consider leaving your resuscitation room, you must ensure that there is no other source of hypotension. This means getting chest and pelvic xrays to look for hemothorax or fractures. It means getting a good FAST exam to make sure there is no significant hemoperitoneum. It also means making sure that any fractures are properly splinted and there is no uncontrolled external bleeding.

You can only go to CT scan once all of these other potential bleeding sources have been ruled out. If in doubt, you must proceed to OR to either stop the bleeding or prove that it does not exist.

Are there any other reasons to take one of these patients to CT that you can think of? If so, leave comments or tweet!

Related post:

Source: The Trauma Professionals’s Blog

Can I Take A Hypotensive Patient to CT? Part 2

In my last post, I commented on a paper that tried to claim that there is no reason not to take a patient to CT if they are hypotensive. It had issues, as you saw. Today, I want to share another paper from a few years ago that tried to do the same. Again, read the abstract!

I’ve said it before: hypotension and CT scanners don’t play together well. For years I’ve cautioned against this, having seen a number of patients crash and burn in this area early in my career. But it’s a common error, and may jeopardize your patient’s safety. A paper that is now in press looked at this practice in a trauma hospital in Taiwan.

Patients who had blunt abdominal trauma were retrospectively reviewed. Those who remained hypotensive (SBP<90) after 2L of crystalloid were scruitnized. The CT scanner was described as being located in the same area as the ED resuscitation rooms. Furthermore, several physicians and nurses were present during scans, and a full selection of resuscitation equipment was available in the scan area.

Here are the factoids:

  • 909 patients were entered into the study
  • Only 91 patients remained hypotensive after initial resuscitation, and only 58 of these were scanned before definitive management
  • As expected, patients who were hypotensive after initial resuscitation had more serious injuries (ISS 22 vs 12), required more blood transfusions (938 vs 202 cc), and had a higher mortality (10% vs 1%).
  • There were no significant differences in comparing hypotensive patients who went to CT scan vs those who did not if they underwent some sort of hemostatic procedure (laparotomy, angioembolization)
  • In the hypotensive patients, time to OR in the CT scan group was 58 minutes vs 62 minutes for those who skipped the scan.
  • In the same patients, time to angio in the CT scan group was 147 minutes vs 140 minutes without a scan first.

The authors conclude that “hypotension does not always make performing a CT scan unfeasible.” (weak!)

Read this paper closely and don’t get fooled! It is very retrospective and very small. And if you look at the times carefully, you will see some funny business. How can time to OR or angio be virtually identical regardless of whether CT is used? Is it the world’s closest, fastest scanner? Probably not.

The authors showed that hypotensive patients have a ten-fold increase in mortality. They also recognized that definitive control of hemorrhage is the key to saving the patients. Unfortunately, there are factors in this retrospective study, such as various biases and some undocumented factors that make their two patient groups look artificially alike. This gives the appearance that the CT scan makes no difference.

In reality, the fact that there is no difference in times ensures that there is no clinical difference in outcome. To really answer this question, this kind of study must be done prospectively, and must have an adequate population size.

Bottom line: Don’t even consider going to CT with hypotensive patients. Even if you have the fastest, closest scanner in the world. Shock time still kills, and most CT scan rooms are very poor resuscitation rooms. If your patient is unstable in the ED, do your ABCs, get a quick exam, then transport to the area where you can get control of the bleeding. This will nearly always be your OR.

Reference: Hypotension does not always make computed tomography scans unfeasible in the management of blunt trauma patients. Injury, in press, 2014.

Source: The Trauma Professionals’s Blog

Don’t Just Read The Abstract: CT Scanning The Unstable Patient

I’ve said it many times before: “don’t just read the abstract.” They can be misleading, and doing so makes it impossible to see the shortcomings of the research model and the veracity of the conclusions. Yet good trauma professionals do it all the time.

So I’ve selected a recent poster child to demonstrate this tenet. Let’s go over the study details:

This paper is a retrospective, registry review from Japan. The authors point out that one of the long-held rules is to avoid scanning unstable trauma patients in the “tunnel of death.” The authors cite a prior study that did not show an increase in mortality from this practice. So they decided to repeat/confirm it using 11 years of national registry data.

They included all patients who arrived at the trauma center with blood pressure < 90. Interestingly, they excluded patients in frank or near arrest. And finally, patients with critical data points missing were excluded. They used a regression method to control for covariates such as age, ISS, and vitals upon arrival.

Here are the factoids:

  • Out of nearly 200,000 patients, about 7,000 were initially eligible. About 1,000 were excluded by the criteria above or because they were treated at a low volume facility. Only 5,809 were included in the study and another 500 were excluded because of missing covariates.
  • The authors found that there were significantly fewer deaths in the group of unstable patients taken to CT (20 fewer per 100 patients) (!!!?)
  • However, when corrected for confounders, this significant difference went away completely
  • But the authors conclusion in the abstract was: “We suggest physicians should consider CT as one of the diagnostic options even when patients are unstable.”

Bottom line: What? The study went from showing that taking an unstable patient to CT was amazing for decreasing mortality, to no different after applying more statistical methods. And since there was no difference, why not just go?

Here’s why. In-hospital and 24 hour mortality are not good indicators of anything because there are so many patient and hospital factors involved. And because it was a registry study, there was no way of knowing if the patient was hypotensive at the time they were taken to CT. They could have had a low blood pressure and responded well to resuscitation. Or they could have been normotensive on arrival and became hypotensive before CT scan. There is no way to cleanly identify the correct study group without a prospective study, or a very painstaking retrospective one.

One of the most important aspects of this study is some background info that is not stated in the paper. Surgeon involvement in initial resuscitation in Japan is not nearly as integrated as it is in the US. So if the resuscitating physicians can’t do anything about the bleeding in the ED, why not just scan them while awaiting arrival of the surgeon? If the patient crashes, was it due to the scan, or a delay in getting to the OR?

So don’t just read the abstract. If it seems to be too good to be true, it is. Or at least self-serving. Read the nitty gritty details and decide for yourself!

Next week: more on unstable patients and the CT scanner

Reference: Computed tomography during initial management and mortality among hemodynamically unstable blunt trauma patients: a nationwide retrospective cohort study. Scand J Trauma 25(1):74, 2017.

Source: The Trauma Professionals’s Blog

The Pan-Scan For Trauma

Diagnostic imaging is a mainstay in diagnosing injuries in major trauma patients. But the big questions are, how much is enough and how much is too much? X-radiation is invisible but not innocuous. Trauma professionals tend to pay little attention to radiation that they can’t see in order to diagnose things they can’t otherwise see. And which may not even be there.

There are two major camps working in emergency departments: scan selectively vs scan everything. It all boils down to a balance between irradiating enough to be satisfied that nothing has been missed, and irradiating too much and causing harm later.

A very enlightening study was published last year from the group at the University of New South Wales. They prospectively looked at their experience while moving from selective scanning to pan-scanning.They studied over 600 patients in each cohort, looking at radiation exposure, missed injuries, and patient injury and discharge disposition variables.

Here are the factoids:

  • Absolute risk of receiving a higher radiation dose increased with pan-scanning from 12% to 20%. This translates to 1 extra person of every 13 evaluated receiving a higher dose.
  • The incidence of receiving >20 mSv radiation dose nearly doubled after pan-scanning. This is the threshold at which we believe that cancer risk changes from low (<1:1000) to moderate (>1:1000).
  • The risk of receiving >20 mSv was lower in less severely injured patients (sigh of relief)
  • There were 6 missed injuries with selective scanning and 4 with pan-scanning (not significant). All were relatively minor.

Bottom line: Granted, the study groups are relatively small, and the science behind radiation risk is not very exact. But this study is very provocative because it shows that radiation dose increases significantly when pan-scan is used, but there was no benefit in terms of decreased missed injury. If we look at the likelihood of being helped vs harmed, patients are 26 times more likely to be harmed in the long term as they are to be helped in the short term. The defensive medicine naysayers will always argue about “that one catastrophic case” that will be missed, but I’m concerned that we’re creating some problems for our patients in the distant future that we are not worrying enough about right now.

Related posts:

Reference: Comparison of radiation exposure of trauma patients from diagnostic radiology procedures before and after the introduction of a panscan protocol. Emerg Med Australasia 24(1):43-51, 2012.

Source: The Trauma Professionals’s Blog

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