Friday, April 8, 2011

Sodium Nitroprusside with CPR

Here's another interesting piece of animal literature to fight with your IRB about for performing studies on human subjects in your ED.  The article itself is a little hard to follow because of the terminology used - eCPR, SNPeCPR, and S-CPR, but, essentially, they have regular CPR, then they have their enhanced CPR which consists of an impedance device and compressive trousers, and then they have enhanced CPR plus sodium nitroprusside.  Additionally confounding, on top of different CPR methods, they only gave standard CPR epinephrine, while the other two methods received no epinephrine.  Sodium nitroprusside pigs did much better than the other two methods and medications.

So, with n = 8, in pigs, there's only a couple statistical conclusions we can make.  Their pigs that received their no-drugs enhanced-CPR did no differently than standard CPR with epinephrine.  Then, their pigs that received sodium nitroprusside plus enhanced-CPR do way better than their no-drugs enhanced-CPR.  So, sodium nitroprusside is doing something.  As far as external validity, 1) it's pigs and 2) it's probably financially and logistically infeasible for our ACLS-equipped paramedics to go through the additional steps of enhanced-CPR.  I'd really like to see what would have happened in a blinded, three-arm, nitroprusside vs. epinephrine vs. placebo where each group had the same CPR.

That being said, if you can get your IRB to approve a prospective study in human subjects - more power to you.  All the literature shows our current ACLS is mostly useless - and the definition of insanity is doing the same thing over and over again and expecting different results - so I'm all for looking at new agents in cardiac arrest.

Thursday, April 7, 2011

Carbapenem Resistant Bacteria in India

More public health doom and gloom from the infectious disease world - multiple bacterial found carrying stable and transmissible plasmids for the NDM-1 gene, a form of beta-lactamase that endows bacteria with carbapenem resistance.  In the sewage.  And in the drinking water.

...but only South Asia, for the time being.  But, they also note that India is a popular destination for "medical tourism" to save money on surgical procedures, and patients have returned as carriers for bacteria with the NDM-1 gene.

This is not a unique development - there's MDR tuberculosis, inducible clindamycin resistance for MRSA, and, my favorite, macrolide-resistant streptococcus.  Macrolide resistance in streptococcus can be directly linked to the overuse of azithromycin, a patient-friendly drug with terrible pharmacokinetics.  In contrast to the medication it replaces, erythromycin, it has such a long half-life (68 hours when multiple doses are administered) after you take your fifth dose that it spends a long period in the body below its therapeutic concentration, just sitting there as substrate to induce resistance without bacteriostatic properties.


Wednesday, April 6, 2011

Antibiotics for Acute Otitis Media

These are two articles coming to us from January's NEJM - one from Pittsburgh and one from Finland.  For a ridiculously prevalent disease managed daily in the ambulatory setting by thousands of providers across the world, we really don't know what we're doing.  Firstly, we know there are bacteria in the middle ear - plenty of studies have aspirated out a variety of pathogens.  Secondly, undertreated AOM may lead to suppurative complications - the surgical emergency of mastoiditis.  Finally, however, we also know the natural history of AOM is to resolve without intervention and treatment in most cases.

The commentary accompanying these articles seemed to think these two studies tilted the balance in favor of routine antibiotic use for AOM.  And, you can read the articles in that fashion - the Finnish article makes an argument that by their standard of care, the placebo group had 45% treatment failure and required antibiotic rescue 30% of the time.  However, I read the article and their definitions of treatment failure are, for the most part, not clinically relevant.  A red ear that still looks red on day three does not predict much - and, actually, a lot of their primary outcome measures were not statistically significant until they added in the 30% they used rescue treatment on to boost their definition of treatment failure.  So, this study doesn't tell much much - except that Augmentin causes diarrhea 40% of the time.

The Pittsburgh study reads much more straightforward and, partially, justifies my criticism of the Finnish study.  By day 7, 80% of their Augmentin group had symptom improvement compared to 74% of their placebo group.  However, the ears still looked terrible in the placebo group - but, obviously, weren't correlating with symptoms.  So, is it clinically relevant to define treatment failure based on the appearance of the ear?  I would say that improvement in symptoms is the appropriate measure of clinical cure - and in that respect, the 80% vs 74% numbers match up better with previously published literature.

To me, these articles don't help.  I don't necessarily mind the AAP recommendations of treating AOM with antibiotics under a year of age - although, really, after their third set of immunizations, it's not as though this is going to be a nidus for SBI.  Clearly, antibiotics offer some advantage - but not to everyone.  When I have a three year-old I have to hogtie to get a one-second glimpse at a red TM, how do I know whether this is a patient whose AOM will resolve on its own, or whether he falls into the subset of patients who will derive benefit from antibiotics?  And, is that 6% absolute difference in clinical outcome worth giving 40% of children horrible diarrhea (not that anyone uses Augmentin first-line for AOM, anyway).  With the NNT with antibiotics to prevent one case of mastoiditis estimated at 4100 from cohort data from the United Kingdom, that's a lot of useless (and harmful) antibiotic prescriptions.  If we want to reduce the amount of antibiotic resistance in this country, I think these studies support a conservative non-antibiotic strategy initially in appropriately selected patients.

Addendum 5/11: Scott Weingart & David Newman did a bit of a rant on this topic on the most recent EM:RAP where they attacked the Pittsburgh article specifically regarding result reporting integrity.  Dr. Newman delved into far more detail regarding the multiple primary outcomes listed and found the original research protocol listed only time to resolution of symptoms as the primary outcome - which was statistically equivalent between the two groups.  He and Dr. Weingart seem to suggest there was not sufficient editorial oversight regarding the publication of this article due to these flaws, and that the author's conclusions are suspect to the point of disingenuous.

Tuesday, April 5, 2011

Mandatory EKG Screening for Athletes

Discussion today in the public forum about this article:

Has been going around the internet.  I only have access to the abstract, however, so I can only base my discussion on what data I see there.  This is one of those articles that reviewed the rate of death in NCAA athletes for the last few years, and, essentially, they found that the incidence of sudden cardiac death was 2.28 event per 100,000 participant years.  The commentary in the media: if only we had better screening!

Well, they tried that in Israel.  Mandatory EKG screening was instituted in 1997 in an attempt to curtain SCD in athletes.  The death rate before screening was 2.54 events per 100,000 participant years.  Afterwards, 2.66 events per 100,000. 

So, yes, if only we had better screening - because EKG alone doesn't cut it.  EKG + echocardiography?  EP study?  At some point, you have to take a rational look at the costs of something and realize it's not taken out of an infinite pool of money - money that almost certainly could be put towards a much higher yield public health effort.  Reactionary calls for more screening at this time are simply increased costs without proven benefit.

Monday, April 4, 2011

Olanzapine Versus Droperidol

This is a fun study because it's always nice to have new things to try for common problems.  Keeps life interesting.

I started out residency taught to use metoclopromide+diphenhydramine for treatment of refractory headache in the Emergency Department.  And then I discovered droperidol.  Yes, there are studies out there that say prochlorperazine is equivalent to droperidol in efficacy, but prochlorperazine gives people the same akathisia that metoclopromide does.  Droperidol kills people dead, if you believe the black box - though I don't.  The QT-prolongation is essentially no different than ondansetron, the supposedly-safe alternative we now use for nausea.

In any event, now you can add olanzapine to your mix.  You can legitimately critique the study because the p-value for pain improvement between olanzapine and droperidol was actually 0.30 in favor of droperidol  - so without more power and/or a second confirmatory study, you can say it really might not be as effective.  But, the good thing is, nearly everything has some legitimate effectiveness - and the more different classes of medication you have available to knock down that headache, the better.

Suntory Yamazaki 12-Year

EM literature, you say?  Well, in addition to reading and critiquing literature, I've begun to enjoy trying new and interesting Scotch, and tonight the tasting is Suntory Yamazaki.

Now, the purists among you are absolutely correct that the Yamazaki is not Scotch - technically, it is a single-malt whiskey - because it is not from Scotland.  Where I'm at in North Carolina, there are government-run ABC stores that all tend to have a generally homogenous selection of the major distributors, with very few "interesting" Scotches.  On my way back from SAEM this past weekend, we walked by an ABC store in Virginia, where, in contrast to North Carolina, the stores are open on Sunday.  Curious to see if their mix was any different than ours, I popped in to look - and picked up this slightly more exotic selection.

I'm not a Scotch snob, so I'm not going to give you a play-by-play of the vanilla vs. cardamom vs. brine-soaked Wellingtons on the palate.  It's either bland, tasty, or delicious with me.  This one qualifies as tasty.  Sweet, pleasant nose, enjoyable finish.  Would not hesitate to buy a reasonably priced bottle from this distillery again.  I'm sure the connoisseurs among you would probably prefer the 18-year, but in the $40-odd range for Scotch-style whiskey, going up against the introductory-level McCallen, Glenmorangie, etc., it won't disappoint.

ASPECT 2-Hour Rule-Out

Low-risk chest pain - if your ED doesn't already have a chest pain unit set up for you to painlessly move patients through their enzymatic and non-invasive testing, you're probably trying to find safe ways to discharge your chest pain patients home to avoid the repetitive calls to an unsympathetic hospitalist.  Problem is, without some kind of imaging or functional study, you're going to invariably get burned.  This is another one of the TIMI-score-plus-X attempts at risk-stratifying patients in a prospectively applied dry run of their protocol.  It's TIMI 0 patients plus normal EKG plus negative zero and two-hour CKMB/troponin/myoglobin.  Basically, 10% of their chest pain cohort fit this essentially zero-risk profile and were enzymatically ruled out.  And 0.9% (0.02 to 2.1%) of this slam-dunk non-cardiac group came back with an MI within 30 days.

Now, for a rational person who thinks that we're spending altogether too much money and resources to capture every last potential cardiac event - that sounds pretty reasonable.  Home with follow-up.  The problem is, the non-invasive testing in basically the same sort of low-risk cohort, whether stress or CTA, the negative tests have 6+ month event-free periods.  So, the standard of care is unfortunately moving away from "no heart attack today!" to prognosticating distant events.

The other great thing about this article was their mini systematic review where they say there's 115 of these prediction rules in the literature in the last fifteen years.  Clearly someone everyone wants, but also something we can't get right....