Dabigatran: Hidden Danger in the Home

The flaws with dabigatran have been well-described on this blog – mostly focusing on its lack of realistic reversal options.  However, less obvious are the unanticipated ways patients end up in situations requiring such reversal.

This case report from the Rocky Mountain Poison Center describes an elderly male on dabigatran who does something commonly seen in the elderly: he suffers acute renal failure from a minor medical illness.  Unlike warfarin, dabigatran is renally excreted, and should not be used by patients with reduced glomerular filtration rates – these patients were excluded from the Phase III trials.  In the presence of renal failure, the half-life increases from 12-17 hours to 18-27 hours, depending on the severity of the renal dysfunction.  This leads to supratherapeutic levels.

This patient was noted to have a dabigatran plasma concentration nearly triple the therapeutic mean and developed spontaneous, unremitting gastrointestinal hemorrhage.  Despite resuscitation, blood products, and emergency dialysis – which halved the dabigatran concentration within four hours – the patient expired. 

Clinicians using dabigatran, therefore, need be acutely aware of any clinical changes in their patients that may reduce renal function.

“Fatal dabigatran toxicity secondary to acute renal failure” 
www.ncbi.nlm.nih.gov/pubmed/23158612

Make Ketamine Work For You

Along with droperidol and dexamethasone, ketamine is on my short list of favorite medications for use in the Emergency Department.  As this correspondence from authors at Highland Hospital summarizes, it’s a floor wax and a dessert topping:
 – Use as peri-procedural pain control/anxiolytic to assist with subcutaneous infiltrative local anesthesia.
 – Use as adjunctive pain control in patients who are failing high-dose narcotics.
 – Use as pain control/anxiolytic in patients with significant supratentorial comorbidities.

These authors state “In clinical practice, chronic pain, psychologic distress, and behavioral disorders frequently overlap”, and I couldn’t agree more.  Sub-disassociative doses of ketamine (0.1 to 0.3 mg/kg) have an excellent safety profile and represent an ideal option for multiple common clinical situations in the ED.

If your ED restricts the use of ketamine, you need to make that stop.

“Emerging applications of low-dose ketamine for pain management in the ED”
www.ncbi.nlm.nih.gov/pubmed/23159425

Ultrasound – For Long Bone Fracture

I have to say, I’m a little confused by all the new SonoSite television ads – direct-to-consumer marketing for sports medicine ultrasonography?  Or for zero-complication central line placement?  Weird.

But, I digress.  A little.  This is a pediatric study of lightly trained ultrasonographers with varying levels of expertise using ultrasound to diagnose long-bone fractures.  They performed 98 ultrasound examinations that were followed up by plain radiography, and they picked up 41 of the 43 fractures present, with 8 false positives:  95% sensitivity and 85% specificity.  Six required reduction, all of which were identified as meeting criteria for reduction on ultrasound – as well as one additional false positive from a distal radius fracture.

As a feasibility study, it’s a nice little pilot.  As a practice-changing strategy, it needs larger sample sizes and external validity.  However, it does seem as though it will soon become reasonable to use bedside ultrasound to quickly rule-out fracture in patients with a low pre-test probability, while plain radiography will continue to play a role in advanced orthopedics management.

“Emergency Ultrasound in the Detection of Pediatric Long-Bone Fractures”
www.ncbi.nlm.nih.gov/pubmed/23114237

All Elevated Troponins Are Not MI

Have you ever received sign-out on a patient, heparinized, awaiting cardiology consultation – and later, at your leisure, realized the troponin level just barely tips into positive territory and probably has nothing to do with acute coronary syndrome?

I know you have.

This is the cardiology “expert consensus” on interpretation of troponin elevations – 25 pages of clinical summary and 360 references worth of dissecting what an elevated troponin really means.  There’s an hour-long lecture worth giving based on this publication.

The key portions include:
 – Figure 1, which is a nice conceptual overview in which elevated troponins are separated into their “ACS” and “non-ACS” categories.
 – Section 6, which discusses the possible role (if any) for troponins in non-ischemic conditions.
 – Appendix 4, the clinical conditions in which positive troponins are non-cardiac and confounding in origin.

Positive troponins need to be evaluated properly in their clinical context, and this is a lovely (if very, very long) reference document for describing it.

“ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations”
www.ncbi.nlm.nih.gov/pubmed/23154053

ECASS III Errata

This is my favorite sort of article to feature on this site – a probably-overlooked letter about a certainly-overlooked feature of a landmark trial.

This author, from Mt. Sinai, notes last year, the authors of ECASS III updated their online manuscript to change a p-value in their baseline characteristics from 0.03 to 0.003.  Since these are p-values for baseline characteristics, they’re only for illustrative purposes – considering, in randomized controlled trials, all the differences do occur by “chance”.  However, the conceptual interpretation of this change in ECASS III is the placebo group was inadvertently randomized to have a history of prior stroke by a 7% absolute difference – and the chance of that occurring randomly has now admitted to be 1 in 300 rather than 1 in 30.  When tremendously unlikely differences in baseline characteristics occur “by chance”, it raises troubling questions regarding whether they truly occurred randomly.

Additionally, the author of this letter also makes the astute point that, because this difference in baseline characteristics did not reach statistical significance by the ECASS III authors’ definition (0.004), it was not adjusted for in their data analysis.  In his adjusted reanalysis (data not shown), the significance of outcomes favoring thrombolysis disappears (OR 1.19, CI 0.89-1.59).  Not necessarily surprising, considering the updated meta-analysis including IST-3 data published in The Lancet also makes the statistical significance of the benefit of thrombolysis disappear past 3 hours.

Thrombolysis for acute stroke remains some of the most distorted treatment data in emergency medicine, where this heterogenous patient population is being overtreated based on “eligibility”, rather than “likelihood of benefit”.

“Implication of ECASS III error on emergency department treatment of ischemic stroke.”
http://www.ncbi.nlm.nih.gov/pubmed/23141561

Don’t ß-Blockade Cocaine Chest Pain

Or, specifically, ignore this evidence that says you can.

There may be some mythology to the hypothesis that non-selective ß-receptor blockade is contraindicated in the setting of cocaine chest pain.  After all, the supporting evidence consists only of small, laboratory case series – and other outcomes-oriented data suggests ß-blockade is cardioprotective, as we already know.  However, this study is a perfect example of inappropriately extending a conclusion from retrospective data.

These authors identified 378 patients from retrospective chart review, selecting patients with chief complaints of chest pain and positive toxicology tests for cocaine.  Unfortunately, urine toxicology tests for cocaine stay positive for days following the initial episode of cocaine use.  Therefore, there is no way from these chart review methods to reliably differentiate the acuity of the cocaine intoxication.  

This is important because a major flaw in retrospective reviews, such as this, is a confounding selection bias.  If all cocaine chest pain patients are not created equal – the neurohormonal effects of cocaine last on the minutes to hours while their drug tests are positive for days – then providers may be selecting patients for beta blocker use/non-use based on acuity information this review cannot detect.  If providers are excluding patients from beta-blockers based on the acuity of their intoxication – as many sensible providers might – and only using beta-blockers in non-acute presentations, then this study may not include any of the population of interest.

The authors’ statement of “We have found that BB use in the acute management of cocaine-associated chest pain did not increase the incidence of MI” cannot be defended as accurate, as it is based on indefensible assumptions.

“Safety of β-blockers in the acute management of cocaine-associated chest pain”
http://www.ncbi.nlm.nih.gov/pubmed/23122421

The Hazards of Love

“Sexual activity is mechanically dangerous, potentially infectious and stressful for the cardiovascular system.”

Indeed!

According to this retrospective review of 11 years of electronic health records from University Hospital Bern, Switzerland, they identified 445 patients seeking emergency care secondary to sexual intercourse.  The majority of emergency department visits were secondary to suspected infectious etiologies (62%), but neurologic complaints, trauma, and cardiovascular incidents comprised the remaining portion.  

The trauma portion probably speaks for itself without need for additional detail.  There was one myocardial infarction and one aortic dissection.  Among the “various complaints”, two patients were diagnosed with “eczema”.  However, among the neurologic emergencies, there were 12 cases of subarachnoid hemorrhage and 11 cases of – ah – “transient global amnesia”.

All things being equal, at least, sexual activity was only associated with 0.1% of emergency department visits – hardly the most dangerous of potential choices of recreation.

“Sexual activity-related emergency department admissions: eleven years of experience at a Swiss university hospital” 
http://www.ncbi.nlm.nih.gov/pubmed/23100321

Viral Testing in Children With Fever

This study attempts to address the question we’ve been asking ourselves since the dawn of antibiotics – does this child with a fever have a viral infection, or a bacterial infection?  Of course, in reality, we should be asking a more complicated question – does this child have a viral infection, or a bacterial infection for which the increased likelihood of positive outcome with antibiotics outweighs the harms of the antibiotics?  But, I digress.

One hypothesis that is bandied about in literature and practice is, if rapid viral testing were available in the Emergency Department, perhaps a positive viral test result would reduce the likelihood of antibiotic usage.  These folks from Washington University performed viral PCR for a host of common viruses on 75 children with fever without a source, 15 children with probable bacterial infections, and 115 afebrile children presenting for outpatient surgery.  The authors note the patients with bacterial infections were less likely to test positive for a virus – and suggest prospective trials might describe a strategy in which viral testing decreased antibiotic use.

In their cohort, 55% of children aged 2 to 12 months and 39% of those aged 13 to 24 months with no obvious source for fever received antibiotics.  This is irresponsible lunacy.  However, a much faster, cheaper way to decrease antibiotic use is:  to simply return from the abyss of antibiotic overuse to a land of rational practice.  

After all, 40% of the bacterial infections and 35% of the outpatient surgical patients tested positive for a virus – clearly indicating the presence of a virus has limited association with acute viral illness or absence of an acute bacterial infection.  More tests are not the answer – at least, certainly not this battery of PCR tests.

“Detection of Viruses in Young Children With Fever Without an Apparent Source”
http://www.ncbi.nlm.nih.gov/pubmed/23129086