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

Comparison of Adult Head CT Rules in Pediatrics

Interesting – if limited in prospective use – retrospective comparison of the New Orleans, Canadian, and NEXUS II instruments for risk stratifying adults suffering minor head trauma.  Busy, urban children’s ED went through 8 years of data to find over 6000 patients with minor head trauma.

Unfortunately, they only looked at the 2,101 that received a head CT, so we lose a huge chunk of our population to “clinical judgement” that could have profoundly affected the specificity of the rules and perhaps had small effects on their sensitivity.

Full of interesting tidbits – 25% of their study population was under 2 years old, but 41% of their injuries were detected in the under 2 population.  Sensitivity and specificity essentially rose and fell with the percentage of the cohort scanned – the New Orleans rule would have scanned 89% of their cohort…that had an incidence of 4.4% of intracranial injury.  That made the sensitivity 96%, but the specificity 11% – and I hate to think what the specificity would have been if the other 4000 patients had been included.  The Canadian Rule scanned the least, missed the most at 65% sensitivity, but achieved a 36% specificity.

But the real question is – what’s the point?  The PECARN criteria get you up to ~96% sensitivity with a specificity of 53-58%.  Kids aren’t small adults – especially infants, and especially in trauma.  Don’t apply adult criteria in kids.

http://www.ncbi.nlm.nih.gov/pubmed/21465153

“Suspended Animation”

This is, actually, an important avenue of contemporary research, highly funded by DARPA at Texas A&M – although this research is from Germany – and this article is about one of the methods tested that got into the lay press a year two back.

The driving principle is that, the best way to keep someone newly dead from starting to go down all those cellular pathways that make cells go “pop”, is to shut down cellular metabolism and starve those pathways of cellular energy.  This seems like a sound idea – although, a lot of other cellular pathways that maintain cellular integrity and electrochemical gradient stability are also funded by those same pathways.  But, the theory is that if you have a tissue hypoxic event, slow everything down to buy you more time, fix the overriding problem, and then resuscitate the patient.

Didn’t work for these folks.  61 Wistar rats given hydrogen sulfide as their agent to paralyze cellular metabolism.  Significantly better pH and less base excess initially during acute resuscitation from cellular hypoxia, so it is doing something to prevent tissue oxygen debt – but their primary outcome of neurologic preservation, they showed temporary neurologic preservation at an interim test, but no differences at the 7 day point, and no histochemical differences after sacrifice.

This sort of research is still clearly poking about in the dark right now, but it is absolutely the future of resuscitation – to give us a reason for hope in the trauma bay that return of circulation is neurologically intact and not simply just for organ donation.

http://dx.doi.org/10.1016/j.resuscitation.2011.03.038

Vital Sign “Triggers”

So, this was an interesting article about a system of vital sign “triggers” an ED implemented to get nurses to flag specific patients for more urgent attention.  Not unexpectedly, the study finds that, when nurses get physician’s attention, everything happens more rapidly to those patients, orders, antibiotics, and disposition.  The problem is, the article doesn’t address the appropriateness or any unintended consequences of this sort of intervention.  The theory would be that these abnormal vital signs represent patients that need more urgent evaluation, but vital signs are always just one piece of the puzzle.  In any event, this study spotlights something that can be reasonably construed as important – nurses should be educated to recognize potentially ill patients and notify physicians.

Of course, in the back of my mind, I was envisioning our ED (and likely many around it) which rooms patients first, and then triages them – and it then becomes the responsibility of the nurse whose zone they have entered to take and record vital signs.  This results in patients being roomed much faster – which many studies have shown is likely a good thing.  Unfortunately, when a patient is roomed to the high-acuity side based on chief complaint, the nurse to which they are assigned may be quite busy with their other high-acuity patients…and that patient may just sit in the room for some time without an assessment or vital signs.

Everything has potential unintended consequences.

http://www.ncbi.nlm.nih.gov/pubmed/21521399

…and Here is Why the Elderly Are Falling

Orthostatic intolerance.

Not much more to say.

An entire quarter of their convenience sample of elderly (mostly female) volunteers had a 60 point drop in their blood pressure upon standing, with only a modicum of recovery within 2 minutes.

Antihypertensive polypharmacy was weakly associated with orthostatic intolerance, and the presence of orthostatic intolerance was weakly associated with an increased number of falls.

So, if the disease (hypertension) doesn’t harm you, the treatment will.

http://www.ncbi.nlm.nih.gov/pubmed/21438868

2005 AHA CPR Guideline Changes Had No Effect

Most recently, the new “hands-only” CPR guidelines have received a lot of press and attention, and there’s a lot of excellent research showing that any intervention that stops CPR decreases survival.  Well, the last time they revised the CPR guidelines, they were also intended to decrease CPR pauses, including changing the manner in which defibrillation was performed, making longer CPR intervals, and eliminating pulse checks after shocks.

The “Resuscitations Outcomes Consortium” did a crossover study looking at survival to hospital discharge before and after the implementation of the new guidelines…and they found no statistically significant differences.  They did find a clinically significant improvement in VT/VF survival that went from 14% to 18%, but the p-value was 0.06 – and it’s hard to attribute that solely to the guidelines because there are other significant baseline differences, particularly a 28% to 34% increase in bystander CPR.

Should be interesting to see if widespread implementation of the new CPR guidelines increase overall or subgroup survival.

The paper also mentions their current studies, looking at whether automated devices improve outcomes and when AED analysis should be performed in sequence.

http://www.ncbi.nlm.nih.gov/pubmed/21497983