CPR ON STEROIDS

CPR on steroidsVasopressin has been advocated in and out of the CPR algorithm. Adrenaline is still hanging in there. And now the Greeks want to add steroids?! In this pretty solid multi center trial, they randomised cardiac arrest patients to standard adrenaline or to adrenaline + vasopressin + the corticosteroid Solu-Medrol. They more than doubled the survival with good neurological outcome!

More on the study below, but first a bit of background. This multi center trial was preceded by a single center study by the same group in 2012, it lives here. It showed better neurological outcome as well as higher incidence of ROSC in the VSE (Vasopressin+Steroid+Epinephrine) group.

There is bound to be some sceptisism towards these findings, as drugs and other interventions have shown promise to enhance CPR before, without being able to reproduce this in later studies or real life. Vasopressin being one of the most recent examples.

Drugs in CPR
Drugs in CPR has been controversial the last many years. Many don’t really believe in them anymore. The focus has been on quality compressions with minimal hands-off time. No drugs have a real, proven benefit in real patients. This article is looking to change that. We’re used to adrenaline (which gives a slightly higher chance of ROSC, but no long term survival benefit), now let’s have a look at the two other drugs and their proposed role in cardiac arrest resus:

Vasopressin is considered interesting for avoiding the beta-effects of adrenaline, and showed promising results in animal studies, with increased coronary flow and oxygenation delivery to the brain resulting in increased incidence of ROSC and improved neurological outcome. Unfortunately, several human studies have been disappointing. This might point to the steroids being the special sauce in this mix.

Corticosteroids have been proposed in cardiac arrest (CA) due to the low levels of corticosteroids in cardiac arrest patients compared to other states of shock or emergency conditions. Also, CA survivors have higher levels of corticosteroids than non-survivors. It is proposed that there is a ‘postresuscitation disease’. Negovsky wrote on this way back in 1972 when we still had the USSR, article here. The theory is that this post-resuscitation disease – a state of myocardial dysfunction, vasodilatation and cytokine badness, somewhat similar to septic shock – can be alleviated by giving steroids. Finally, steroids can also enhance the body’s catecholamine response.

Read all about these and other meds that might have a place in cardiac arrest in this great overview article – written by the same Greek team that did the VSE studies.

The study
This latest study is a double blind placebo-controlled study. Patients were eligible if they had an in-hospital vasopressor-requiring cardiac arrest in one of the three hospital centers. Patients were randomised into receiving either adrenaline only (control) or adrenaline with vasopressin and a steroid (VSE group).

The 138 patients in the VSE group were given adrenaline 1 mg/CPR-cycle in accordance with CPR guidelines, but were also given vasopressin 2o IU/CPR cycle and a single dose of 40 mg methylprednisolone. The 130 patients in the control group were given adrenaline 1 mg/CPR-cycle and placebo instead of vasopressin and methylprednisolone.

Screen Shot 2013-08-19 at 5.48.08 PM

Main outcomes were return of spontaneous circulation (ROSC) for 20 minutes or more and survival to discharge with a cerebral performance category score (CPC-score) of 1 or 2.

Results
Screen Shot 2013-08-19 at 5.39.37 PM83,9% of the patients in the VSE group achieved ROSC of 20 minutes or longer.
66% of the patients in the control group avhieved ROSC of 20 minutes or longer.

To treat the ‘postresuscitation disease’, shock after resuscitation was treated with stress-dose hydrocortisone 300mg for up to 7 days.

Patients in the VSE group also had a higher propability of surviving to discharge with a favourable neurological outcome (CPC-score of 1 or 2) compared to the control group. 13,9% vs 5,1%.

The future of CPR?
So, does this work? The two randomised trials presented here say it does. And not on animals, but on humans. Real patients and hard outcomes. This even convinced Dr. Weingart to consider adding VSE to his CPR mix. And why not? The evidence is as good as for any other meds we give during CPR, and these trials certainly look promising.

Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial, JAMA, July, 2013.

Current pharmacological advances in the treatment of cardiac arrest, Emerg Med Int, 2012.

Dr. Weingart’s VSE Emcrit Wee is of course also worth a listen here

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6 Responses to CPR ON STEROIDS

  1. Mike says:

    I was researching for CPR related topics and found this excellent post. Just dropping by to say thanks! 🙂

  2. Tor Pedersen says:

    Interesting – and widely published – study… But it does have some significant weaknesses. Multiple interventions = black box, so what worked? The intervention and control groups also have important differences, many which favor the intervention group, most importantly there was significantly more asystoli as first rhythm in the control group. There were also differences between the groups in rates of PCI-treatment, and also not all patients were given therapeutic hypothermia, not a signficant difference between the groups, but it increases the risk of selection bias.

    And with the RCT’s for epi vs no-epi showing no effect on survival to discharge, and the negative effect of epi on neurological outcome shown in Hagihara’s enormous (n=417000!) retrospective study… shouldn’t the control group have been no-epi?

    • Thomas D says:

      Thanks for your comments! I agree that it’s unclear what worked in this study, but the authors seem to claim that it was the cocktail – all the meds in synergy – that worked, and studying one drug at a time wouldn’t make sense if you look at it that way.

      Regarding differences between the groups, there were the same number of VT/VF patients (the ‘easy’ saves), a higher number of PEA’s in the intervention group and a higher number of asystole in the control group. So there is an unbalance, but probably not that big for outcomes. Hard to tell, but a legit critisism.

      No-epi in the control arm would probalby have people say you’re comparing VSE to placebo, and that epi was the active cocktail ingredient. Also, since epi is still the standard in CPR, it could be hard to hold it from the control arm. Doing studies on epi vs. no-epi in cardiac arrest has always been controversial (even if it shouldn’t be).

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