Cite this post as:
Scott Weingart, MD FCCM. EMCrit Wee – Vasopressin, Steroids, and Epinephrine for Cardiac Arrest. EMCrit Blog. Published on August 2, 2013. Accessed on April 19th 2024. Available at [https://emcrit.org/emcrit/vasopressin-steroids-epinephrine-for-cardiac-arrest/ ].
Financial Disclosures:
Dr. Scott Weingart, Course Director, reports no relevant financial relationships with ineligible companies.
This episode’s speaker(s), (listed above), report no relevant financial relationships with ineligible companies.
CME Review
Original Release: August 2, 2013
Date of Most Recent Review: Jan 1, 2022
Termination Date: Jan 1, 2025
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Interesting study for sure. I am unclear why they elected to only give steroids post-ROSC if the pt was in shock.
I believe they did give other vasopressors prior to the 4 hour mark as defined by what they called “post resuscitation shock” (sustained, new post arrest circulatory failure or post arrest need for 50% or greater increase in any pre arrest vasopressor/inotropic support…)
You are correct though. It seems difficult to deduce this piece of information.
This is certainly a compelling study, but not sure what we can do with the results. While we all know that epi is “standard care” all over the world for cardiac arrest, epi has only been shown to increase ROSC, not RONF. I would love to see this study repeated with VSE vs no epi (or even better, a good 3-arm RCT with VSE vs epi vs placebo). This study just seems like it shows that 3 meds that don’t work are better than 1 med that doesn’t work.
Trueg-
VSE vs. placebo would be rather useless if you think it through logically. VSE 3 arm would be reasonable, but doubtful it would ever be done. Why don’t you get the properly powered epi vs. placebo done.
Unless you have stopped using epi during your arrests, then you know exactly what to do with the results. Have you stopped giving epi?
What role is solumedrol playing during the arrest? The onset time is at least an hour in most cases…I’m confused by this…
The other thought provoking thing here, the dose of steroids following ROSC, I have to wonder if it’s neuroprotective by reducing swelling, and or ICP. It seems like very high dose of Vasopressin…120IU? I know the AHA reccomends 40IU once, and I’m all about challenging the dogma..is vasopressin better than epi?
dose of vaso was 20IU
For clarification
The purpose for the Solu-Medrol is to reduce swelling? By what mechanism? Sorry if this is a basic question, just a pre-med.
Adam,
The mechanism is probably more so via a “stress response” i.e. using corticosteroids for adrenal insufficiency in the setting of refractory hypotension.
I like the study, and the implications…from my perspective (as a paramedic), Solu-Medrol would be an easy drug to add to a resuscitation, given that we carry it already for RAD/anaphylaxis. And I like the idea of pre-empting reperfusion injury. That said, I’d be interested to see the effects of single-dose versus tapered doses…it’s sometimes (read: often) very difficult to get multiple EMS systems and hospitals on the same page for post-resuscitation care in my neck of the woods. I’m not sure what the implications of single-dose intra-arrest Solu-Medrol without tapered-dose in ICU would be….any thoughts?
Since they only started the continuous steroids in patients with post-arrest shock, a bunch of them only got the single dose of solumedrol so we can imagine there may be benefit (though as you said, it would be great to see a study actually proving that).
My default prejudice is that vasopressin doesn’t offer any long-term survival advantages and that steroids are kind of a catch-all treatment for any sort of (sometimes critical) illness, whose use often exceeds any proven indications. From the start, I’m a bit biased in that my plausibility level is low… Unlike, say, Rivers’ work where I think the simple act of bundling treatment is actually an important intervention, I really wish they hadn’t combined the treatments here because both therapies seem somewhat unlikely from the start. In larger studies, vasopressin has been shown to offer no real survival advantages in humans… Read more »
Vince, Your points are all true and well made, but I think I see studies like this slightly differently. We both agree that a superior study would have been simply epi vs. epi + steroids (or a three arm with a placebo arm as Trueger would like). But obviously the authors believe (their hypothesis) that vasopressin is bringing something to the table. So that is how they did their two studies. Since they did, all we can say is VSE is superior to epi alone IF we believe in the internal validity of the trial. I’ve seen no arguments to… Read more »
Thanks for the thoughtful response! I agree that my point in the section you expressed confusion about was poorly defined. Thankfully you helped lead me where I wanted to go by later stating, “The Bayesian responsibility is on the part of the interpreter not the researcher…” which is the only real discussion point where I think we diverge (probably since the foundation of my understanding of EBM was forged from your book…). While it’s true that a portion of the Bayesian analysis will always fall on the interpreter, I happen to believe that we are at the point where a… Read more »
I’m with Adam and Ryan, what’s the pathophysiology behind using steroids in cardiac arrest? Plus, it takes about 45 minutes to take affect…
I think, as Ben alluded to above, it’s the massive SIRS response after the global ischemia-reperfusion. The authors reference their own prior study in 2009 (the initial spyros et al in annals of internal medicine, jan 2009 12;169(1): 15-24). In that study, the intro + discussion goes over why they chose intra-arrest + post-arrest steroids, and they do a good job of citing prior evidence/support. To loosely paraphrase, the intra-arrest dose was thought to augment post-arrest perfusion pressure, and the post-arrest steroid was essentially used to treat the post-arrest syndrome similar to a “sepsis-like syndrome”. Because of that, they used… Read more »
I think the big problem here is that they were in hospital arrests. We (in the ED, at least in our set up) don’t look after in hospital arrests. From my time as an intern and ICU doc, responding to all the cardiac arrests in the hospital, they were a very different population from the out of hospital patients. I suspect (though as I write this I realise i should really do a pub med search first) that there’s a lot less VT/VF and the big killers are PEs, electrolyte disorders and post op sepsis. Vasopressin/steroid might be the drug… Read more »
thanks for the comments. very useful! Andy, I am surprised by your request for bigger numbers! 18 v 7 is over double intact neuro survival! How much bigger numbers do you want? In an arrest patient population!!?? I find the skepticism remarkable in some of the comments and yes Trueger and I debated this online. This is the second +ve RCT for this Rx bundle. There are a heck of a lot of Rx we do that have much less supportive evidence : Prehospital cervical spine immobilisation comes to mind, cricoid pressure ( yes I will admit that one even!),… Read more »
hang on..my only theory why there is some skepticism to this paper..is that some ..(maybe many) of us have stopped using epinephrine in cardiac arrest care..and this paper suggests that was a wrong decision…and this causes sufficient cognitive dissonance to adopt the position. ..that this paper is wrong..rather than the decision to stop using epi in arrest ..was wrong instead
right?
I agree somewhat. This actually was a follow-up on a 2009 single-center study by the same authors – also well done. Ideally, it would be replicated by different authors to be totally above reproach (and they need to separate steroids and vaso, as discussed above), but I think we might be able to start applying this. We would do that mostly out of knowing epi by itself doesn’t really work, and trying other various ways to augment perfusion pressure (particularly during the transition from intra-arrest to post-arrest) may be helpful. It seems like there are a couple different aspects of… Read more »
Most of my own skepticism boils down to the fact that we’ve not only been burned a few times by steroids for several disease states, but also oversold on “lifesaving” cardiac arrest interventions in the past. Combining the two sounds like a great way to set up an evidence-based minefield and I fear we’ve been down this path before… The authors did the right thing by chasing their initial data, but results that more than double favorable outcomes sound way too good to be true unless we get these interventions verified by an independent set of investigators. Individual practitioners are… Read more »
thanks Trent, agree.
One thing. Epi does work in arrest..it just doesnt work enough by itself!
Consistently improves ROSC in past studies of arrest care…just not RONF!
I’m so glad you have posted on this paper Scott as I read this one and have been hanging out to see what debate could come of it. My default position is that a) anything showing a new set of drugs in cardiac arrest is useful will probably be misleading and b) any new intervention that looks good in medicine usually starts to look pretty awful shortly afterwards when it has been studied a bit more. That said, I couldn’t really fault this study. There were two primary outcome measures which really means you are getting a second lottery ticket… Read more »
Hi, Just a thought, but I think RFDSDOC’s post highlights a good point: the arrest population offers a unique study group in that a majority of patients who arrest die, so there are no major harms that we can do with these medications (except for ROSC without RONF, which is no small issue) that would warrant being overly cautious about their use. In fact, these treatments have all been used, albeit not as a bundle, and so it seems to me we could produce a lot of data just by using this treatment algorithm in a larger population. Granted, I… Read more »
thanks for the additional useful comments here!
in fact no one commenting has given a single good reason NOT to follow VSE Rx in hospital arrest situations.
And for all those who stopped giving epi in ACLS, then some reconsideration on that stance is warranted!
The evidence based medicine door swings BOTH ways!
I would say that people who are already using epi should consider vse, those who believe in not using it may choose to ignore this study.
Ah, so this is where the discussion brews.
I didn’t like this article. I do have issues with internal validity, re: baseline differences between groups, different follow-up interventions, the multiple interventions, and confounding associations with good outcome. It also troubles me this is the same group x2, rather than independent verification.
There is the issue of “well, ain’t they dead?” but I’d rather be more confident in the cognitive outcomes before I start VSE during arrest – unless my goal is simply keeping the husk alive for organ harvest – before I start a multi-day ICU pathway of resource utilization.
I guess the ? I ask you Ryan is do you still use epi. If the answer is no, then your points are entirely consistent with your practice. If you are using it, how do we justify that drug?
Great discussion as always.
Thanks scott.l totally agree with you , If you believe in epi why not go ahead for VSE & give it a shot.
A large study whether 2 or 3 arm RCT would be of intersest to validate these results.
As RFDSDOC said EBM doors swing both ways.
Thsnks.
Hi Scott and all involved in the discussion re this paper. I have a slightly different issue with the results and presentation of them. While the numbers certainly look favourable for the VSE group and any benefit is welcomed in this area of practice, my issue is with the other treatments given and the baseline survival rates. Firstly, no patient in either the control group or the intervention group appears to have received defibrillation (Table 2) despite the fact that almost 17% of cardiac arrest rhythms in each group are reported as VF/VT and that over 90% of arrests in… Read more »
There’s a small trial from the 1980s where dexamethasone was given prehospital as a single dose. Seems underpowered though. Only about 45 patients in each arm. Plus they did some other weird stuff too, MAST trousers, etc.
Annals emerg med vol13 issue 11 November 1984
Having practiced as Paramedic, CCCP, and APP for 38 years, what I find most interesting and puzzling is the process that the AHA employs in setting protocol policy. If you look at the study selection process, it’s just not impressive at all. Frankly, I find the lack of long term well defined trials employed, after all these years, frustrating to say the least. There is enough evidence to warrant investigating the notable E-V combined outcome effect, and the E-S-V combined outcome effect by either replicating the initial positive outcomes or setting them aside. I believe that further studies will support… Read more »