Category: Resuscitation

Essentially, no ACLS medication therapy has been shown to be terribly efficacious with regard to meaningful patient outcomes.  Epinephrine – if we could find a way to satisfactorily preserve neurologic and cardiovascular status after return of spontaneous circulation – seems to have a small helpful effect, but has all sorts of deleterious effects on LV function and cerebral perfusion.  Otherwise, nothing is proving useful other than CPR, shock ventricular arrhythmias, and hope for the best.

I posted about this back in April, and it’s another article – from the same masters of porcine resuscitation up in Minneapolis – about a second series of protocols they used to evaluate “sodium nitroprusside enhanced CPR”(SNPeCPR).  The CPR is the same.  The SNPe part is multiple doses of IV sodium nitroprusside and an impedance threshold device, along with a more limited role for epinephrine administration.

They ran two protocols for this study.  Protocol A was a ventricular fibrillation model with 6 standard CPR pigs, 6 CPR + impedance threshold, and 12 SNPeCPR pigs.  Protocol A favored ROSC in SNPeCPR – 0/6, 0/6, and 12/12.

Protocol B was a PEA model with 8 pigs of standard CPR vs 8 pigs of SNPeCPR.  Protocol B favored ROSC in SNPeCPR – 0/6 vs. 7/8.

I think they might be onto something here, but I am still a little wary about the results because both these articles are from the same institution and they keep using these idealized perfusion platforms.  Other investigators should heed this research to evaluate whether their methods are externally valid and warrant human trials.

“Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models”
www.ncbi.nlm.nih.gov/pubmed/21725236

There is a physiologic phenomenon observed in animal studies that a small increase in plasma osmolarity using hypertonic saline increases microperfusion, including myocardial and cerebral blood flow.  Therefore, in theory, hypertonic saline administration during resuscitation from cardiac arrest should be efficacious in improving survival and neurologic outcome.

These authors conduct a randomized prospective trial in which they prove that 100 patients in each arm is not enough to make valid claims about a secondary endpoint for which the study was not designed to evaluate.  There is no difference between groups in mortality – and not even non-significant trends – but a small, significant, absolute difference in neurologic impairment, 4.9% without neurologic impairment in the control group and 13% in the intervention group.

So, another study suggesting further study is needed.  If anything, it demonstrates how impossibly hard it is to evaluate treatments in the heterogenous population of out-of-hospital cardiac arrest, and to ensure internal and external validity.

“Randomised study of hypertonic saline infusion during resuscitation from

The crux of the problem – epinephrine continues to improve short-term ROSC with uncertain long-term outcome improvement.

This is a prospective out-of-hospital arrest study from Australia in which epinephrine or saline placebo was given to patients during resuscitation by EMS.  And, like many studies before it, it fails to show a meaningful difference between patients receiving epinephrine and patients receiving placebo.  Rather, their primary outcome of survival to hospital discharge had 1.9% with placebo and 4.0% with epinephrine – but this result was not statistically significant with a p-value of 0.15.

Of course, what the lack of statistical significance means in this case is that this difference could have occurred by chance 15 times out of 100 times they performed this study – which, while not meeting the gold standard of 5 out of 100, is still a reasonably interesting clinical trend.  Like all studies before it, the short-term endpoints met statistical significance, including ROSC of 8.4% for placebo and 23.5% for epinephrine.  There are a few confounding differences between groups: more placebo patients had witnessed arrest, although the number with bystander CPR was the same; more placebo patients were endotracheally intubated in the field, which usually confers a survival disadvantage; and more epinephrine patients were ultimately transported to the hospital from the field.

So, there’s two ways to look at it: 1) epinephrine works, and we just need to figure out how to salvage more of those ROSC or 2) epinephrine is flogging far too great a number of lost husks back to life that will go on to consume ICU resources and expire regardless.

But, if we’re not going to give epinephrine, how do we otherwise look busy during a code?  And, what happens downstream to our epinephrine ROSC that fail to leave the hospital or the ER, and can we prevent it?

I am still not sure what the right answer is – like many diseases, cardiac arrest patients are a heterogenous group in which there is almost certainly a subset of patients that benefits from epinephrine, but we don’t yet know who that might be.

“Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.”
www.ncbi.nlm.nih.gov/pubmed/21745533

Thanks to @cliffreid of Resus M.E! for first noting this article.

All our cardiac arrest patients roll in these days with an IO in place – and we are full proponents of rapid, successful access in the uncontrolled field environment.  But, how effective is it really in the CPR situation?

So, this is an animal study that tries to address the theoretical efficacy of intraosseous access versus central venous access.  They use injection of dye tracers into Yorkshire swine for a comparison between intraosseous sternal, intraosseous tibial, and external jugular central venous cannulation.

Unfortunately, this is a good news/bad news study.  The good news – peak concentrations were achieved only slightly more slowly in the arterial circulation following sternal intraosseus injection than the gold standard central venous injection.  And, the peak concentrations were nearly identical.  Bad news, the tibial IO was half the speed and half the arterial peak concentration of the sternal IO.

In theory, this is of relative importance depending on which medication you’re using – presumably the speed of administration matters in CPR and peak concentration may matter as well.  Of course, this is limited as 1) pigs and 2) efficacy vs. effectiveness, because they’re not measuring clinical outcomes.

But it’s interesting to worry about.  Too bad it’s hard to do chest compressions with your access point where your hands are supposed to go.  It would be interesting to compare this result to a humeral head IO.

“Pharmacokinetics of Intraosseous and Central Venous Drug Delivery During Cardiopulmonary Resuscitation.”
http://www.ncbi.nlm.nih.gov/pubmed/21871857

I like that the big focus these days is on increasing cerebral perfusion pressure in cardiac arrest – sure, we can focus on more interventions to flog the heart back into coordinated activity, but, sometimes, it’s just not going to happen.  But, for when we are able to get the heart rolling again, unless you’re a big organ donation proponent, we need to preserve neurologic outcomes.  After all, that’s where a lot of our studies of ACLS fall off – we get short-term ROSC, but survival to hospital discharge is unchanged because the brain is unrecoverable.

Here’s another trick in pigs – sustained AA pressure resulting in measurable increases in CPP.  Better CPP = better neurologic outcomes in other studies.  Seems like a no-brainer.

I particularly like this intervention because it’s basically no-cost and should be easy to test for outcome efficacy in humans.

http://www.ncbi.nlm.nih.gov/pubmed/21550162

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.