Is it still cool to cool in cardiac arrest? The new TTM Hypothermia trial! #FOAMed, #FOAMcc

So the other dayI read the TTM trial (http://www.nejm.org/doi/full/10.1056/NEJMoa1310519?query=featured_home#t=article) with great interest, as cardiac arrest and the post-resuscitation phase have always been among my pet topics.

First of all this is a big trial.  Bigger that the previous ones that established hypothermia as a standard of care. Does it obviate those previous results?  Absolutely not. Those trials were not 32/33 vs 36 but 32/33 vs “whatever happens.”

Hypothermia makes a lot of sense physiologically, but of course that doesn’t mean that it might not have some harmful side effects that have not yet been clearly delineated (besides the current known hemodynamic ones and relatively benign electrolyte and renal alterations).

However, it is pretty clear that, compared to 33 degrees, 36 does just as well, which leans towards saying that all we have to do is avoid fever, or stay in a very mild hypothermia.

Avoiding secondary injury in brain pathology is key (no desat, no hypotension, and no fever), and in anoxic encephalopathy, it is no different.  The key thing is that in this trial, the temperature was controlled – ie it would not be acceptable to do no cooling, and just chase the fever (which is very common) with acetaminophen, which would invariably result in significant time spent above 36 (oops, tylenol didn’t really work, ok lets put the blanket, etc …this is gonna be hours).

So is this the end of aggressive cooling?  Not necessarily.

For anyone interested in the topic, I suggest reviewing Peter Safar‘s data on dogs and cold aortic flushes – it is absolutely unbelievable to see dogs who  had an arrest, got the cold aortic flush (brain temp below 10 degrees), are left stone cold dead for 45 minutes, then resuscitated and are then able to go around a few days later and do doggie things like run and bark and eat…  So I don’t think that cooler isn’t necessarily better, but that we haven’t yet delineated what are the pros and cons of each temperature range or how to get there practically and safely.

So what should we do?  Well, it would seem reasonable to do either at this point, and accepting a temp between 32-36 (I have usually preferred 33-34 as they rarely drift down into the 20’s as I’ve seen the 32’s do) as being adequate. This may make hemodynamics a bit easier to manage in certain cases.
Also check out Scott’s take at:
 http://emcrit.org/podcasts/emcrit-wee-targeted-temperature-trial-changes-everything/#comment-58635
And the RAGE Podcast addresses this topic at about 25 minutes:
…and of course, keep abreast of further data and subgrouping that may become available on this, and further trials. But for now, its definitely still cool to cool, maybe just a little less…

Steroids for cardiac arrest…really? My take on the VSE study – #FOAMed, #FOAMcc

So I’ve been asked a few times for my opinion about the VSE study in the last couple of months, so here we go.

JAMA2013;310(3):270-279. doi:10.1001/jama.2013.7832.

First of all, lets look at it from a theoretical perspective.  How would steroids contribute to ROSC (return of spontaneous circulation)?  Hard to believe they possibly could, given the ultra-short timeframe to ROSC – minutes mostly – and the much longer action of steroids.  However, it is quite possible – and in view of this study perhaps likely – that there is an effect on shock and RONF (return of neurological function).

Why?  Post arrest shock results in MSOF due to a cascade of inflammation resulting from the hypoxic insult. Remember that we are not designed to survive these events. Being designed to fight off moderate trauma and infection (eg being bitten by an animal or clubbed by another caveman) our physiological reaction often overshoots the mark resulting in more damage than good, as it does in sepsis (variably depending on our different geno/phenotypes).  So whether liver, kidney or brain damage, some component is not only related to pure hypoxia but also to an inflammatory cascade that has a prolonged effect. This is the same thing we are targeting with cooling, on top of a simple metabolic supply/demand issue, so in terms of biological plausibility, it makes some sense.

In the post-ROSC phase, there is always the possibility of relative adrenal insufficiency – after all, the adrenals have taken a hit as all the other organs did – so again there is biological plausibility.

There’s quite a bit of debate out there as to whether or not to apply this.  I’m pragmatic, not a purist, and my beliefs lie in evidence, biological plausibility and the risk/benefit ratio.  In this case, I think the decision is actually quite simple.  The way I see it, the steroids are harmless and probably helpful, so I have been giving solumedrol in the last few months.

If anything, I’m more concerned about the harm I may be doing with epinephrine/vasopressin, especially in terms of RONF.  I do hope an epi (various doses) vs placebo study is done, because it is difficult to withhold, knowing that there is greater immediate effect on ROSC… Hard decision as the clinician at the bedside, and hopefully this will become clearer in the near future.

For those unclear about the whole epi debate, the physiological issue is that the relationship between pressure and perfusion is represented by an inverted U curve – at very high pressures (from vasoconstriction) perfusion is decreased (think of the extremities on high dose pressers with a decent BP).  So although we may help coronary perfusion pressure and thus ROSC, end-organ damage is greater…and nothing matters much without a brain.

 

So bottom line:  I’d go ahead with the steroids, and for now the V and E, but I wouldn’t be surprised to drop or decrease those soon.

More to come on resuscitation and its future (the present for some of us…) in posts and podcasts!

Hope this helps!

Philippe