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Sunday, April 20, 2014

Part 2: Does Cyanokit save lives in cardiac arrest?

In the last post I reviewed some key facts about hydroxocobalamin (HCB), otherwise known by its brand name Cyanokit. However, paramedics and firefighters aren't really concerned with the animal studies - they want to know if it saves human lives! 

And according to some flashy headlines, many people believe this stuff works when nothing else can.

But these are news reports and press releases - what does the medical evidence show? 

Does HCB help in cardiac arrest due to smoke?
This is the tough hurdle for studying any toxicologic antidote, and it's especially hard to do research in this area. The events are rare, and it's usually an emergency when these poisoning occur. For these reasons, and more, there have only been a few studies of HCB in humans.

Four studies have looked at the use of HCB in smoke-exposed patients. Interestingly, 3 of them were done in France, mostly in Paris.

Just for fun, Google "Paris" and "burning."

Study #1 - All smoke exposure patients who got HCB  

The authors of the first study looked at all the patients treated with HCB over an 8-year period  for "suspected cyanide poisoning" after a smoke inhalation, usually from a house fire. It's important to understand that there was no comparison group so it is impossible to know whether the drug helped, hurt, or did nothing.

With that in mind, all 101 patients got HCB, and all were from residential house fires; about 1/3 of those were in cardiac arrest. Forty two patients died, 30 survived, and the status of 29 patients was "unknown.

How about patients found in cardiac arrest? Of the 38 patients who where found in arrest, 21 of those had prehospital ROSC - pretty encouraging. Unfortunately,  the majority of those (19/21) subsequently died in the ICU.

This might be encouraging if we were givne some data about those 2 out of 38 patients who survived. For instance, did they get the HCB before, during, or after their cardiac arrest? Unfortunately, there are no further details

Study #2 - All cyanide exposures who got HCB

Just like the study above, the authors of study #2 included patients with smoke inhalation or cyanide ingestion who were treated with HCB by EMS. Since this was written by the same authors as study #1 above,  and covers mostly the same period (1995-2008), it is likely that many of these patients overlap with those in the prior study.
Out of the 161 patients studied, 61 were found in cardiac arrest. Most of these died in the field, or ended up dying in the hospital, but 5 patients lived after getting HCB from EMS!

That's an 8% save rate, which seems very promising, but the authors note that most of these "saves" didn't actually get HCB before they had ROSC. As they point out (my emphasis):
"Among the 61 patients in [cardiac] arrest, 5 survived without sequelae and, in particular, without neurological sequelae. Four of the 5 patients were ... discovered in cardiac arrest by the fire brigade, and spontaneous cardiac activity was obtained after cardiac massage and oxygen therapy. ...
[H]ydroxocobalamin was not responsible for the recovery of spontaneous cardiac activity in these patients."
I'll point out that the 5th cardiac arrest survivor had his age only listed as "adult," suggesting that the EMS records were incomplete, at the least... 

Study #3 - All smoke exposures, who got HCB, and who made it alive to the ICU
The last study adopted a slightly different approach. The authors performed a retrospective "observational case series" of all of the patients who who had smoke exposure, received HCB in the field, and were subsequently admitted to the ICU

A total of 69 patients were enrolled. Of these, 15 patients had been in cardiac arrest when EMS found them. Of these 15 patients, only 2 survived.

Hey, 2/15 is a 13% save rate, which might be really promising. Or might not be - we can't tell from the study design.

Study #4 - All smoke exposure patients who got HCB - in Texas! 
You might not have thought that Paris and Houston would have a lot in common!

You can skip Googling "Paris" and "Houston"
As it turns out, both Parisians and Texans have been using HCB for years, and a just-published abstract describes the experience of the FD in Houston. Unfortunately, the study wasn't "Texas-sized," and was actually smaller than those done in Paris.

Like the French studies, the Houston authors looked retrospectively at all the patients who had received HCB for "possible cyanide poisoning." Over a period of 4 years, 22 patients got the drug. Half of those were found in cardiac arrest, and 8/11 had ROSC "after administration of HCB."

So, awesome, right? Unlike study #2 above, the patients in cardiac arrest actually got HCB before ROSC, not after. Is this proof that HCB, given in arrest, can produce ROSC rates in almost 75% of cases? 

 Limitations of these "case series"studies
Unfortunately, we still can't say.  All of these studies were basically case series. It is very low-quality evidence, ranking just above expert opinion. You can think of such a study design as just a fancy doctor phrase meaning "a bunch of cool stories."

Why? Because there is no comparison group in any of them. Since the drug was never actually tested against another drug, let alone a placebo, we don't know if HCB helped, or did nothing

Heck, for all we know, it may have even hurt patients. We just don't know.

 So, what can we do with this data?
By itself, not much. HCB is a new therapy, with potential, but no solid human evidence to support when we should use it. Of course, we don't always wait for perfect evidence to come along before using drugs and therapies.

With that in mind, what should you and your teammates do the next time FD drags a patient in cardiac arrest out of a fire? Or what if one of your firefighter teammates collapses next to you during a fire?

The next post will offer some suggestions, based on better evidence, of techniques and therapies that have been shown to lives.


  1. Brooks,

    I am in the process of writing a more detailed response that I plan to post tomorrow. In the meantime, my answer is yes. I would administer the Cyanokit to a patient in cardiac arrest that has been removed from a burning building. I would also administer it to a patient that is not in cardiac arrest but 1) is presenting with signs of cyanide toxicity in conjunction and 2) has a lactate greater than 6mmol.

    As for a firefighter, this is a different story. If they collapse during a fire, I don't presume the etiology is from cyanide toxicity. Traditional therapies here. If they are found with either a broken mask or not wearing their mask at all, I would then add it to their treatment.

    Regardless, more to follow.


  2. I'll await your longer response! Thanks for reading.

  3. My post is too long...and the footnotes got all messed up in the copy/paste process. Email instead?

    1. Brooks.walsh_at_gmail. Looking forward to this mega-response!

  4. WIth such goodies as acrolein, cyanide, phosgene and others, both as gasses/vapors and adsorbed onto micro-particles of soot (which reach alveoli and are phagocytized) even in "common" household fires, this should be studied properly. My respects to the French, but they tend to announce too early. (mycrofft)

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