Saturday, May 19, 2012

Azithromycin - Not Guilty of Murder

The FDA has announced it is reviewing the safety of azithromycin in lieu of a recent NEJM article documenting an association between azithromycin and cardiovascular death.  In theory, azithromycin has been implicated in QT-prolongation and pro-arrhythmic effects, leading to torsades de pointes and polymorphic ventricular tachycardia.  The authors of this study therefore hypothesized an association between azithromycin use and cardiovascular death.

This is a retrospective study of computerized data generated from the Tennessee Medicaid program between 1992 and 2006, linking deaths to any concurrent antibiotic prescriptions.  The authors data-mined for a cohort aged 30 to 74 years of age, had no "life threatening non-cardiovascular illness", did not abuse drugs, and did not reside in a nursing home.  They compared azithromycin prescriptions to non-prescription controls, as well as amoxicillin, ciprofloxacin, and levofloxacin cohorts.  And, after a little statistical maneuvering, they report a death rate of 85.2 per 1,000,000 courses of antibiotics with azithromycin, which compares to a death rate of 29.8 with no antibiotic and 31.5 with amoxicillin.

So, for every ~20,000 prescriptions of azithromycin written, there is one additional death from cardiovascular causes.  This is another one of those cases where the severity of the absolute difference doesn't quite match the relative difference - it is likely any efficacy difference between a macrolide and a second-line agent results in greater morbidity than the magnitude of effect found in this study.

Then, azithromycin is frequently prescribed for upper and lower respiratory tract infections - conditions that, in the absence of other specific signs, might be non-infectious cardiovascular disease misdiagnosed as having an infectious etiology.  In their non-propensity matched cohorts, 50% more azithromycin prescriptions were written for respiratory symptoms than amoxicillin.  The propensity matching in their statistical analysis attempts to account for this, but 30% of their azithromycin prescriptions had no documented indication - which I think means there's likely a hidden statistical difference in underlying pathophysiology secondary to unknown indications.

Finally, this runs contrary to a 2005 article "Azithromycin for the Secondary Prevention of Coronary Events" published in NEJM - at one point, it was theorized that azithromycin would be protective for coronary events.  For 4,000 patients who took azithromycin weekly for a year, there was no difference in cardiovascular outcomes as compared to placebo (CI -13% to +13% relative risk reduction).

There are lots of reasons not to prescribe azithromycin, but this study isn't the one that should change your practice.

"Azithromycin and the Risk of Cardiovascular Death"
http://www.nejm.org/doi/full/10.1056/NEJMoa1003833

Thursday, May 17, 2012

The Papermate Flexgrip Cricothyroidotomy

Emergency Medicine has more than a little MacGyver instinct to it - and one of the semi-urban legend aspects of EM is the ability to perform a cricothyroidotomy as a life-saving measure in any situation.  The most commonly described version is performed using simple, commonly available tools - any sort of cutting blade and a hollow tube, such as a hollow pen.

Several studies have approached feasibility by describing the flow dynamics of various pens, but this is the first study to evaluate the procedural feasibility of bystander cric.  This is an observational, cadaveric study using non-EM junior physicians and medical students in which they used a 26-blade scalpel and a Papermate ballpoint pen of 8.9mm external diameter to attempt an "off-the-cuff" cric.  The 9 participants attempting 14 procedures were successful 8 times, although complications were frequent, including vascular and muscular/cartilaginous injuries.

Whether this is externally valid to the living, or to patient-oriented outcomes of effective ventilation, I'm not so certain - but, then again, if the alternative is 100% mortality via no possible ventilation, it's a fun study to see.

"Observational cadaveric study of emergency bystander cricothyroidotomy with a ballpoint pen by untrained junior doctors and medical students"
http://emj.bmj.com/content/early/2012/05/04/emermed-2012-201317.short

Tuesday, May 15, 2012

Reducing ED Overcrowding Reduces Mortality


In Western Australia, in 2008, a mandate was undertaken in which Emergency Departments were to implement processes requiring patients to be discharged or admitted within four hours of presentation.  These rules phased in through 2009 in the tertiary hospitals, and then in 2010 in the secondary hospitals.

Of course, with an arbitrary mandate to simply "work faster," the concerns were that this would have adverse effects on mortality.  Rather, the overall mortality of patients admitted through the Emergency Department tended to decrease during this time period.  Each of the hospitals spent less time of ED diversion ("access block") as well.

The article doesn't mention specifically what process changes were implemented, but it does allude to and likely understates the resistance met while making ED overcrowding a problem for the entire hospital.  Authors report that shifting patients out of the Emergency Department led to a greater proportion of the initial investigations being performed on the inpatient wards, leading to some professional stress.

Regardless, this article seems to suggest that it is feasible, in a culture accepting of change in practice pattern, to decrease the amount of time patients spend in the Emergency Department.  It also seems to demonstrate it is, at least, potentially safe.  That being said, it would be quite a feat to accomplish something similar here in the U.S., given the various warring incentives at work in our highly dysfunctional system.

Emergency department overcrowding, mortality and the 4-hour rule in Western Australia"
www.ncbi.nlm.nih.gov/pubmed/22304606

Sunday, May 13, 2012

Codeine, Potentially Unpredictably Lethal


Frequently used in the pediatric population, codeine is a narcotic analgesic in prodrug form.  In the body, codeine is metabolized to morphine through the CYP2D6 pathway.  In the general population, it is estimated that approximate 10% of codeine undergoes conversion to morphine.

We're generally familiar with the concept that a certain percentage of the population is ineffective at metabolizing codeine, and therefore receives no additional analgesic effect.  However, the flip side, as these authors report, is a CYP2D6 genotype of over-metabolizers.  In this case series, the over-metabolism of codeine in three post-surgical children likely resulted in supra-therapeutic conversion to morphine, leading to respiratory arrest.

The short summary - when possible, avoid medications that are unpredictably metabolized - such as codeine.

"More Codeine Fatalities After Tonsillectomy in North American Children"
www.ncbi.nlm.nih.gov/pubmed/22492761