Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

Does a Placebo vs. Adrenaline Study Deprive Patients of Necessary Care According to the Resuscitation Guidelines?


 Some in the media have been critical of the upcoming British study of adrenaline (epinephrine) vs. placebo for cardiac arrest.[1] They assume that the guidelines require that we give adrenaline, but that is not true.

The guidelines only state that adrenaline may be considered.

If you are a dog, pig, or rat in a laboratory and you have had an artificially induced cardiac arrest, then adrenaline will help resuscitate you. If you are a human who has a cardiac arrest for any one of a variety of reasons, then there is not a good reason to give this rat resuscitation drug, which has not been adequately studied in humans.

There probably are some human patients who do benefit from adrenaline in cardiac arrest, but we have no idea which patients those are and there probably are humans who are harmed by adrenaline. The most common cause of cardiac arrest is heart attack, but you were having a heart attack while still alive, is there a worse drug we could give you than adrenaline? Does adrenaline suddenly become sugar and spice and everything nice, just because we cannot feel a pulse? Maybe, but should we assume that?

What if you have lost so much blood that your heart is not able to produce a pulse, even though your heart is beating as hard as it can? Adrenaline is indicated according to the same guidelines. Why? Unreasonable optimism.

Which patients benefit from adrenaline? We don’t know.

Which patients are harmed by adrenaline? We don’t know.

How do we find out? Research, such as the upcoming study of adrenaline (epinephrine).

What do the guidelines say about conducting this research?
 

Given the observed benefit in short-term outcomes, the use of epinephrine or vasopressin may be considered in adult cardiac arrest.

Knowledge Gaps

Placebo-controlled trials to evaluate the use of any vasopressor in adult and pediatric cardiac arrest are needed.[2]

 

Vasopressors are adrenaline, vasopressin, norepinephrine, and phenylephrine. We need evidence to find out if any of them work.

When the 2010 guidelines were written there was an inescapable need for placebo studies.

Has anything changed?

No.

There was a placebo study in 2012 that was aborted by pressure from media and politicians before any useful results could be obtained.[3]
 

There is evidence that adrenaline improves the return of a pulse, but that appears to just produce comatose patients who die in the hospital without waking up, so the initial improvement appears to be very misleading.

We could try real medicine, where we find out what the right treatment is and give the right treatment to the right patient, but that seems to be asking too much for some people.
 

The Media are Just As Bad at Ethics As They are at Science

Footnotes:

[1] The Controversy of Admitting ‘We Do Not Know What Works’
Wed, 13 Aug 2014
Rogue Medic
Article

[2] Part 8: Advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.
Morrison LJ, Deakin CD, Morley PT, Callaway CW, Kerber RE, Kronick SL, Lavonas EJ, Link MS, Neumar RW, Otto CW, Parr M, Shuster M, Sunde K, Peberdy MA, Tang W, Hoek TL, Böttiger BW, Drajer S, Lim SH, Nolan JP; Advanced Life Support Chapter Collaborators.
Circulation. 2010 Oct 19;122(16 Suppl 2):S345-421. doi: 10.1161/CIRCULATIONAHA.110.971051. No abstract available.
PMID: 20956256 [PubMed – indexed for MEDLINE]

Free Full Text from Circulation.

[3] Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL.
Resuscitation. 2011 Sep;82(9):1138-43. Epub 2011 Jul 2.
PMID: 21745533 [PubMed – in process]

Free Full Text PDF Download from reanimacion.net
 
 

This study was designed as a multicentre trial involving five ambulance services in Australia and New Zealand and was accordingly powered to detect clinically important treatment effects. Despite having obtained approvals for the study from Institutional Ethics Committees, Crown Law and Guardianship Boards, the concerns of being involved in a trial in which the unproven “standard of care” was being withheld prevented four of the five ambulance services from participating.

 

In addition adverse press reports questioning the ethics of conducting this trial, which subsequently led to the involvement of politicians, further heightened these concerns. Despite the clearly demonstrated existence of clinical equipoise for adrenaline in cardiac arrest it remained impossible to change the decision not to participate.

 

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Comments

  1. As I commented at one of the news sites running a story on this trial: Epinephrine in cardiac arrest has been an experimental treatment for ~50 years now. The problem is that there hasn’t ever been a control group, and nobody has bothered collecting the data.

    It is long past time that we stopped this foolishness, and did the experiment the right way.

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