Month: May 2011

Heart Fatty Acid Binding Protein

A nice comparison of the sensitivities and specificities of the various biomarkers for acute myocardial infarction at ~3.5 hours after symptom onset.  Each biomarker was set at the 95th or 99th percentile based on manufacturers definitions for their reference table, and then they also show ROC curves and calculate AUCs for each.

Essentially, none of the biomarkers is completely adequate for ruling out AMI given the constraints of their study.  Their best combination, for both sensitivity and specificity, is combining the heart fatty acid binding protein and the troponin – which they state provides an NPV of 95.6%, outperforming the “triple rule out” of troponin, CKMB, and myoglobin at 92.1%.  Interestingly, they also state that if they used clinical risk stratification, they could select a population in which HFAP and troponin together get up to 96.9% NPV…showing that regardless the resources we throw at the problem of “low risk chest pain”, it is an absolutely Quixotic quest to definitively rule out every MI in the Emergency Department.  3% of their “very low risk” population that was biomarker negative with the best sensitivity they could muster ended up ruling in for AMI during their subsequent hospital stay.  They only way we’re going to prevent healthcare from becoming bankrupt is increasing our levels of acceptable risk.

As a side note, this article gets the award for “best vs. least professional” title so far this year.

http://www.ncbi.nlm.nih.gov/pubmed/21561701

Near-Daily Updates

The presence of near-daily updates is somewhat an artifact that I’ve had an easy time finding interesting research papers to queue up, plus I’ve been in a bit of a lull regarding clinical responsibilities.

The eventual goal will probably be to have something up 3 to 5 days a week from myself, and, if other clinicians start contributing, then, even more than that.
Speaking of which, if you’re at least a senior resident in Emergency Medicine, have opinions, and like writing little blurbs about new literature, you’re welcome to drop a comment regarding potentially contributing to this blog.

Cardiac Arrest – Never Bathe Again (in Japan)

Or, alternatively, never bathe in fall and winter.

Data mining expedition evaluating the event rate of out-of-hospital arrest where activity could be determined, and then using the Japanese averages of time-per-day to evaluate for hourly rates of arrest per activity.

Working was the most cardioprotective per hour spent – and it had the best ROSC and survival, mostly because it was highly witnessed.  Sleeping and exercising were riskier behaviors than working – sleeping moreso, because it was infrequently witnessed and had minimal survival.  So, you might as well just keep working.

But, definitely don’t bathe because 1) no one is watching you bathe, so the survival is dismal and 2) the risk of cardiac arrest was a preposterous 40 times greater than working, and when the time of year was taken into account, bathing in cold winter months led to up to 100-fold increase in arrest rate.

The authors believe this is specifically related to Japanese homes being poorly insulated, leading to predictable large blood pressure drops when entering their traditional very hot baths.

Work harder, live longer.

http://www.ncbi.nlm.nih.gov/pubmed/21543146

Difficult Intubations and Association With Complications

Retrospective data out of the ketamine vs. etomidate prospective survival study.

Doesn’t prove anything – and it makes me want to go back and look at the original ketamine vs etomidate article to see if difficulty of intubation was included as a demographic factor – and, I wish this study indicated which sedative medication was used as well.

In any event, the more complicated an intubation was, the more likely there were complications with the intubation.  And, further down the road, more patients who had intubation complications were deceased at the end of their follow-up period.  Things that predicted complications during procedure included age, illness severity, BMI, specific medical disorders, respiratory distress, and difficult intubation.

Nothing here changes practice – since intubation is not an elective procedure.  This is more a recognition that, yet again, sick people die.

http://www.ncbi.nlm.nih.gov/pubmed/21345571

NSAIDS Kill – Especially Diclofenac

While the protections for individuality make America the colorful place it is today, it sure is easy to run massive cohort studies in European countries where they sacrifice a little bit of anonymity for the common good.

Everyone in Denmark has a number, and they tracked every patient in Denmark with a history of MI to see if they had any adverse events after receiving a prescription for NSAIDs.  There were a few significant differences in the populations receiving each different kind of NSAID – rofecoxib and celecoxib tended to be given to older, female populations, and there were some differences throughout their groups regarding the prevalence of other co-administered cardiac medications.

This article really annoys me because the page with which they present their incidence of death by week has six charts that lend themselves immediately to visual comparison – but their chart scales are grossly different.  Ibuprofen looks terrible at first glance, but then you realize it has the smallest y-axis scale, and actually performs quite well.  In the end, they all demonstrated worsening of outcomes regarding death/MI compared to the total study population rate of death/MI not proximate to NSAID use.

In the end, ibuprofen and naproxen had the least effect on the OR for death; it is fair to avoid rofecoxib, celecoxib, and diclofenac in your routine prescribing without specific indications.

http://www.ncbi.nlm.nih.gov/pubmed/21555710

Erythropoietin is of No Benefit in STEMI

I have to say, the outcomes of this study both surprised and did not surprise me.  A couple years ago, I read a few articles regarding erythropoietin administration in animal models of myocardial ischemia, and they actually tended towards cardioprotective effects.  However, there have been some other retrospective reviews looking at erythropoietin levels in humans that have not been quite as conclusive.

The efficacy cohort rather favored the intervention group – the most important significant difference was primary vs. rescue PCI, and significantly more EPO group patients received primary PCI.  But, then, their results section is mostly a long list of non-significant differences, and some secondary outcomes favoring placebo.  Adverse events also favored placebo.  So, I don’t think we’ll be seeing EPO on the code STEMI order sheet anytime soon.

As another aside, and sort of a follow-up to the Annals of Internal Medicine article a month ago regarding conflicts of interest in the new ACC Guidelines – the disclosure list for this article is massive.  It is clearly the standard of care in Cardiology to be on the payroll of multiple pharmaceutical companies in one fashion or another.

http://www.ncbi.nlm.nih.gov/pubmed/21558517

Advanced Life Support – Not Dead Yet?

Meta-analysis of published trials, 9 for trauma and 9 for non-trauma met their inclusion criteria after review, examining OR for survival when comparing ALS to BLS.

Trauma, unsurprisingly, derives no benefit from ALS in cardiac arrest.  They even found a pooled OR of 0.89 for survival with ALS, but the CI just barely crosses 1.

But, contrary to the two most recently published prospective trials, their meta-analysis of non-trauma arrest still shows a survival benefit for ALS.  They do include a few trials from before AEDs were available in BLS in 1995, but it still doesn’t explain the entire benefit.  They also cite a few studies in which a physician is part of the paramedic team, which may mean there’s more to ALS than AHA ACLS, so that might be a bit of a confounder.  Hard to know what to make of this data, considering the lack of demonstrable benefit from ACLS medications and the decreased survival of patients intubated in the field in out-of-hospital arrest.

My take is still that cardiac arrest, for the moment, is still a place where significant out-of-hospital resource investment is low yield, and CPR and AED is all they need en route to the ED.

Computerized Resuscitation in Severe Burns

This is a critical care study that showcases an interesting tool developed for ICU resuscitation of severe burns.  The authors make the case that adequate resuscitation for burns, i.e., the Parkland Formula, is necessary – but that patients are frequently over-resuscitated.  Rather than simply settling for the rigid, formulaic crystalloid infusion over the first 24 hours, they developed a computer feedback loop that altered the infusion rates based on urine output.  Think of it as insulin drip protocol or heparin infusion protocol – but instead of glucose or PTT, you’re measuring UOP and adjusting the fluid rate dynamically on an hourly basis.

I like this study because they have a primary outcome – improved adherence to their UOP target – and then secondary outcome variables that matter, mortality, ICU days, ventilator-free days.  While secondary outcomes are hypothesis-generating tools, making a rational leap to connect the association between their UOP adherence and the massive improvement in mortality demonstrated would not be reproachable.

It is not a large study – and the control group had the same % BSA burn, but had significantly more % full thickness burns.  The magnitude of the mortality outcome could certainly be affected by more demographics than they report, so a follow-up is necessary.  However, the premise of a feedback loop offloading cognitive tasks from providers as part of the management of a complex system is almost certainly something we’re going to see more of in medicine.

http://www.ncbi.nlm.nih.gov/pubmed/21532472

Augmentin Is Non-Inferior to Appendectomy

A lovely study out of The Lancet that tells us what we already know…is not as right as we thought it was.  We’ve all seen the pediatric patient, usually female, that went to their pediatrician’s office with abdominal pain, had evidence of cystitis on a UA, and was prescribed amoxicillin or cephalexin.  They got a little better, but they’re still having some nausea, some pain, and some loose stools.  In your ED, the ultrasound is positive for free-fluid without visualization of the appendix, and a CT scan subsequently shows evidence for appendiceal rupture.  But – as we’ll see here – most cases probably resolved before you saw them.

This is a prospective study randomizing patients to antibiotics versus early surgery, and the antibiotic group here actually had a lot more success than we imagine – since all we see/remember are those patients where we discovered the “latent” appendicitis, partially treated and festering after that initial course of antibiotics.  Only 12% of their CT-proven uncomplicated appendicitis went on to have a appendectomy in the first 30 days, and 30% within a year.  So, you could almost argue that with an 88% short-term cure rate with antibiotics and a 70% medium-term cure rate, antibiotics should be first-line therapy with observation for clinical worsening.

Definitive therapy has its advantages – you could almost equate the appendix to the gallbladder, and say that the 30% recurrence is almost certain to rise in subsequent years.  But, is there an advantage to waiting to do an appendectomy on an elective basis?  Are the adhesions that might develop more or less of an issue that the risks associated with emergent surgery?  And, of course, in the female pelvis, any undertreated appendicitis represents a significant fertility risk.  This study raises great questions about whether we should change our practice regarding our approach to appendicitis, and it might just be we find a role for being less aggressive with surgery.

“Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial.”
http://www.ncbi.nlm.nih.gov/pubmed/21550483

2010 ACLS Guidelines

I’m sure you’ve seen summary articles from various sources regarding updates to the ACLS algorithm for 2010.  The change in the BLS component from an A-B-C to a C-A-B with a focus on providing high-quality compression-only CPR is well-publicized.

On EM:RAP – an educational resource I simply cannot recommend highly enough as a way to mix entertainment with CME – Mel Herbert issued the challenge to submit proof of the “epinephrine-free code”.  They made this hypothetical challenge based on a close reading of the new ACLS guidelines for PEA/asystole – which, if you look closely, reflect a tacit acknowledgement of the futility of ACLS medications.  Between atropine, bicarbonate, epinephrine, and calcium – various pieces of the kitchen sink available in the code cart – only epinephrine still has a role in the guidelines, but the level of evidence has decayed to IIb, which is at the “expert opinion or consensus” level.

There are a couple large studies with limitations from Scandinavia that show associations of epinephrine with poorer outcomes, or no improvement in survival with ACLS medication administration pre-hospital.  And, if you consider the vasoactive properties of epinephrine – sure it increases CPP, but its effects on the oxygen-debt of the peripheral vascular bed, the effect on subendocardial perfusion and infarct size – imagine giving epinephrine to a STEMI patient.  We’re injuring the most important organ system of interest in cardiac arrest.  I am more than willing to take up the challenge of epinephrine-free resuscitation – I just need to find some evidence to support something else to give in the meantime so I’m not reported to the Chief of Staff so it looks like I’m trying.  Anyone have anything in mind?

http://circ.ahajournals.org/content/vol122/18_suppl_3/
http://www.ncbi.nlm.nih.gov/pubmed/12104107
http://www.ncbi.nlm.nih.gov/pubmed/19934423