Resuscitation – Page 8 – Emergency Medicine Literature of Note

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

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

“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

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

Early Recognition of Massive Transfusion

From trauma resuscitation, a Chinese study trying to predict who will need massive transfusion after trauma. They have a 7-item scoring system retrospectively derived…and it’s probably not terribly helpful.

It’s a nice idea, considering there’s only so much blood readily available in the bank, and a lot of massive transfusion protocols are 1:1 with FFP and sometimes platelets, so advance warning based on the initial clinical evaluation would definitely be helpful. There are some interesting pieces of information in the paper, although, I wish they had all their OR listed for massive transfusion, as opposed to just the ones that shook out from their stepwise regression. Their highest predictor for massive transfusion – a hemoglobin < 7 g/dL with an OR 45.7. SBP < 90 and positive CT or FAST were also predictors with useful OR. Their rule is a little unusual for a theoretically beneficial intervention (massive transfusion), as they focus on specificity rather than sensitivity – probably due to a need to conserve blood component products.

In the end, though, I think most folks with a hypotensive trauma patient whose FAST is positive and a Hgb < 7 could clinically predict massive transfusion as well as this rule does.

http://www.ncbi.nlm.nih.gov/pubmed/21458905

Adrenal Insufficiency in Pediatric Shock

This falls into the “don’t use etomidate” pile of literature. Well-demonstrated, primarily in the pediatric literature, that etomidate and its association with adrenal insufficiency results in poorer outcomes in shock. This article doesn’t look at etomidate, but rather it describes relative or absolute adrenal insufficiency in pediatric shock, and finds it relatively pervasive. It then finds an association between their two definitions of adrenal insufficiency and length of stay, length of ventilator days, and required doses of vasopressors. They only 5% mortality in their study, so they can’t comment on any mortality association.

So, this is another study that helps describe why etomidate may be contributing to poorer outcomes. The days of ketamine + rocuronium RSI are coming (we’ll save the succinylcholine vs rocuronium debate for another day).

http://www.ncbi.nlm.nih.gov/pubmed/21336126

Out of Hospital Arrest Score Validation

There are nice studies in the U.S. defining and validating a rule that determines which patients are unlikely to have ROSC or survival to hospital discharge, e.g. BLS-TOR. This is a study from France that looks at people who do have ROSC to see, not just if they’ll survive, but survival where the patient is not severely disabled or vegetative. One of the nice things about Europe is that their cultural perception of “life” really has to do more with living, and not just simply “being alive”. So, whether we can actually implement something like this in the U.S. may be difficult.

It’s a chart review, which limits its quality to some extent. The other real issue I have with this OHCA score is its complexity – it incorporates initial rhythm, no-flow and low-flow intervals, and admission levels of creatinine and lactate. The U.S. validation cohort had 34% therapeutic hypothermia, which is pretty good – the derivation cohort was only at 11%. Predictors of good neurologic outcome, consistent with other articles: ventricular fibrillation, bystander CPR, lower creatinine and lactate.

Unfortunately, for this rule to get up to 100% specificity, the sensitivity drops to 19%. Alternatively, you could say that’s 20% of out-of-hospital arrest ROSC that shouldn’t have further intervention, which would be an important cost and medical resource utilization savings.

So, this is something that your colleagues in critical care are going to use to discuss prognosis, although I’d like to see something along these lines that helps attenuate the number of people we resuscitate until our post-resuscitation care demonstrates much, much improved outcomes.

http://www.ncbi.nlm.nih.gov/pubmed/21494106

Norepinephrine is Superior to Dopamine

Last day of Journal Club for April.

It is very interesting how generational medical practice is – currently training physicians are accustomed to using norepinephrine for virtually everything as the vasopressor of choice (except, well, when there’s a medication shortage like this past month), while previous generations have a comfort zone with dopamine.

This is a very nice study in a lot of ways and it does a good job if illustrating that dopamine and norepinephrine have very small but relevant clinical effects. Some of their inclusion criteria are a little odd – hypoperfusion/decreased CVP after only 1000mL of crystalloid or 500mL of colloid? And 246 of their patients suffered from hypovolemia due to acute hemorrhage – so you can really question why anyone was reaching for a pressor instead of a Cordis or the OR – and, there are a few other instances with small numbers where neither dopamine or norepinephrine is your vasopressor of choice (e.g., anaphylactoid shock, spinal shock).

But, they had good randomization and their treatment groups are very similar. And what did they find? No difference.

Well, not completely true – no difference in ICU mortality with a p = 0.07 in favor of norepinephrine and no difference in in-hospital mortality with a p = 0.24 favoring norepinephrine. So, norepinephrine is favored, but statistically the results are not bulletproof. I think the trends are reasonable, but it’s certainly worth keeping an open mind. Alternatively, if you wanted to never use dopamine again, you can definitely argue that norepinephrine is no worse.

Secondary outcomes generally trend in favor for norepinephrine with a few reaching significance – although, when you look at 20 secondary outcomes, you’re bound to find some significant differences. The most important difference is the incidence or arrhythmias, primarily atrial fibrillation, which occurred in 24% of the dopamine group and 12.4% of the norepinephrine group at a p = <0.001.

It’s an important paper to have around to be on the same page as the critical care colleagues.

http://www.ncbi.nlm.nih.gov/pubmed/20200382

Emergency Response Teams

This is an idea that sounds great in theory – if you have a roving team of skilled resuscitation professionals in your hospital assisting nurses who are concerned about their patients, you can intervene on these patients before they deteriorate, keep people from escalating into the ICU, and improve outcomes. It’s such a great idea that the entire country of Australia has been spurred into implementing these. My hospital has them, and, no doubt, many other hospitals do as well.

The problem is, they’re having a hard time demonstrating their efficacy.

A study out of Stanford last year reported that, at their VA hospital, implementation of emergency response teams (ERTs) reduced mortality. Unfortunately, on closer reading, ERTs reduced mortality on the floor, and their primary intervention was to move people to the ICU – where their mortality was no longer counted in the study. While it is rather graceless to have people coding and dying on the floor, unfortunately they did not show the outcomes they claimed.

http://www.ncbi.nlm.nih.gov/pubmed/20624835

This more recent report, from Australia, as mentioned above, is a before and after analysis of hospital-wide mortality, CPR rates, etc. with their ERTs. They likewise show benefits, with ICU admissions, CPR rates, and mortality all declining after implementation. However – and they very astutely point this out themselves – one of the most significant functions of the ERTs was to clarify code status and affirm a greater number of people as DNR or futile resuscitation. While this function, if it reduces ICU admissions, is absolutely a cost and resource savings, I don’t think it’s precisely how they wanted to justify implementation of ERTs.

There are many reasons to have ERTs, but a mortality and cost-benefit justification has not yet been well-demonstrated.

http://www.ncbi.nlm.nih.gov/pubmed/21411218

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.

http://www.ncbi.nlm.nih.gov/pubmed/21358401