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Wednesday, April 16, 2014

Cyanokit: What's the evidence? (Part 1)

Cyanide is a very, very potent toxin. I'm not sure this needs more emphasis, especially after two recent examples in the news (from upstate NY, and from a little closer to home). 

Just a quiet suburb? (source)
Hydroxocobalamin (HCB) is an FDA-approved antidote for cyanide poisoning (brand name Cyanokit). It isn't new, having been used for years in France, but there has been lots of talk about it in the U.S., especially for treating patients who have inhaled smoke; e.g. in a house fire.

First step in treating smoke inhalation:
Do not park ambulance in the fire! (source)

There are other antidotes for cyanide, such as sodium nitrite or sodium thiosulfate, that have been available for years. The appeal of the "new" drug, HCB, is that the dosing is somewhat simpler, and there are perhaps fewer adverse effects (at least compared to sodium nitrite).
 
Second step in treating smoke inhalation:
Remove patient from a burning ambulance! (source)

But the interest in HCB doesn't just have to do with dosing or side effects, but also a number of well-publicized and exciting accounts of miraculously revived patients. However,  there are still questions about when to use it, and what the evidence is.


In this 3-part series, I'll review the basic and clinical evidence for HCB. In order to get a fuller picture, I also spoke with a number of paramedics, firefighters, and physicians. I also was able to discuss the evidence with EMS physicians around the country, as well as a number of toxicologists. This group included, of note, not one but three dual-trained firefighter/MDs

Okay, five things you should know about HCB...

1. It's pretty effective - if you're a dog.
The field of toxicology, in general, relies on a lot of basic science and animal studies. It's just too hard to conduct the controlled human trials that would be expected in other fields.

HCB has been studied in a number of animals - pigs, dogs, and even rabbits. I'll just give one example. In a study of beagles getting intravenous cyanide, researchers gave either HCB or placebo. They waited to give the drugs until the dogs had been apneic for 3 minutes. Despite this "head-start" for cyanide, none of the dogs who got the high-dose HCB died, whereas 80% of the untreated dogs died. 


This suggests suggests a strong benefit for HCB, (at least for dogs who are shooting up cyanide).

2. Then again, so is epinephrine (if you're a pig).
Another group of researchers took three groups of pigs, and gave them IV cyanide infusions, up until the point of cardiac arrest. Group #1 of pigs got one dose of HCB, group #2 got epinephrine, and group #3 got nada.

The nada group (#3) didn't do well - all of those pigs died, despite CPR. On the other hand, almost 3/4 of the pigs in both the HCB (#2)and the epi (#2) groups survived.

The authors noted that other measures, like lactate, troponin, and pH, all showed benefit for HCB. Nonetheless, HCB and epi looked just about the same for survival, and both were literally better than nothing!

Okay - anybody want to read more animal data?
"We would prefer to see the human data, if it's all the same to you."
Moving on then - How does this work in people?

3. It appears safe in human volunteers.
When HCB was given to human volunteers, not much happened. There was a small bump in the systolic BP, about 20 mm Hg, and a few minor allergic reactions. The most dramatic reaction was a "skin redness" seen in almost all the subjects who got HCB.



This rash took up to 2 weeks to resolve in some cases! Not dangerous, but certainly something to be ready for. It also turned the urine and tears the same color.

4. It's expensive!
This much is clear - it costs $$$.
Source
Whew! Over a thousand bucks. 

By contrast,  IV amiodarone costs about $20 per code, while a ResQPOD will set you back about $100.  On the other hand, tenecteplase, a fibrinolytic drug that is proven to save lives in STEMI, costs about $1500 a shot.

By contrast, the older drug, antidote sodium thiosulfate is relatively cheap.
Source

5. HCB might save human lives...
$1000 might be worth it, or even cheap, if this drug can save lives. With that in mind, we'll take a look in the next post at the evidence "from the field."


To be continued...


2 comments:

  1. Interesting article. I work in Harrisburg, PA, and have been trying to spread the word of cyanide in smoke and campaigning for Hydroxocobalamin to be added to the approved pre-hospital drug list for Pennsylvania. We've seen the drug for under $800. Also, if you haven't done so already, check out the Fire Smoke Coalition's website www.firesmoke.org. There is a lot of info available including success stories on people.

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  2. Thanks for reading Dan! You obviously have a great interest in the subject, and I hope these articles are of some assistance to you and your brothers & sister in the fire service.

    Yes, I agree that there are a number of dramatic accounts, on a variety of websites, of lives saved with HCB. Of course, these are no substitute for proper clinical evidence.

    The question of whether the available clinical evidence supports this will be the subject of part 2 of this series - be sure to check it out!

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