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How Do You Confuse Two Lethal Injection Drugs? We Asked a Pharmacologist

In a January execution, officials in Oklahoma used potassium acetate instead of potassium chloride...what's the difference?

Science is often a complicated subject, but when it comes to lethal injection, the science is actually the simple part of the equation.

On Thursday, an investigation by The Oklahoman revealed that the lethal injection given to a prisoner in Oklahoma in January didn't follow state protocols. Instead of giving Charles Frederick Warner a lethal dose of potassium chloride, as the protocol requires, records show executioners injected Warner with potassium acetate. Warner reportedly said "my body is on fire" as he died, a process that took 18 minutes.

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In the wake of the news, Oklahoma Governor Mary Fallin has put a hold on all state executions until officials can sort out what happened. The controversy only adds onto the already swirling debate over whether another drug used in execution processes, midazolam, is safe and effective.

The nuances of the ethical and legal questions in this debate are complicated, but the science behind it all is pretty straightforward. David J. Kroll is a molecular cancer pharmacologist, a former university professor, and a freelance science journalist. He walked us through the effects of all the chemicals used in a lethal injection, the questions about midazolam, and what the difference between potassium chloride and potassium acetate even is.

MOTHERBOARD: First off, what is the difference between potassium chloride and potassium acetate?
The difference is very subtle. Approximately the same dose of potassium chloride or potassium acetate will effectively kill a person and the reason is that the active constituent is the potassium itself. It's just really a salt, which means you have a positive charged substance (the potassium) and a negative charged substance (either chloride or acetate).

The average person would recognize sodium chloride is table salt. If you like salt and vinegar potato chips, you will have experienced sodium acetate, which is just a salty version of vinegar. The sodium is still there. It might taste a little different, but if you were to look at your blood stream it would have the same increase in sodium as if you ate the same amount of sodium chloride.

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So since the potassium is still there, from an execution standpoint, it's no different?
It's just a type of potassium. So while the name looks different, the key element in there is the same.

What are these drugs usually used for?
The number one use for potassium chloride is to supplement potassium lost when a person with high blood pressure is taking a diuretic, or "water pill," that works on the kidney so you pee more. In fact, some patients are given potassium tablets to take by mouth since they lose so much in the extra volume of urine they pass. Potassium chloride can also be used for any kind of dehydration due to nausea or vomiting or poor nutrition, or if someone has diabetes or kidney problems, because the kidneys in particular control how your body regulates the sodium and potassium balance.

Potassium acetate is around but it's not commonly used in regular medicine. I talked to a few doctors about this, and they said it's most often used for people who can't eat. When you put the stuff directly in someone's veins: vitamins, sugar, other salts, amino acids—everything you're missing because you can't eat—a lot of those come in the chloride form, so you don't want to add the extra chloride with the potassium. So they use potassium acetate instead in this very specialized situation.

"The body can still have reflex reactions to pain"

How does potassium kill a person?
We need potassium to live, but the body keeps very low concentrations of potassium in the blood. Most of it is inside of muscle cells. But if you screw with that balance of the potassium inside and outside of the cells you can affect muscle activity. An high enough injection of potassium will cause the heart to go into cardiac arrest.

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If potassium is the "lethal" part of the equation, what are all these other drug injections for?
The idea is to use a barbiturate, a dose of a muscle-blocking agent, and then potassium. The whole idea is: first you put the person to sleep, second you paralyze their muscles, and third you paralyze their heart and all other muscles with an overdose of potassium.

We know that first step is now achieved in Oklahoma using midazolam. How does it work?
Midazolam is a benzodiazepine, which were discovered by a chemist in the 1960s who was looking for a safer alternative to barbiturates. What barbiturates did was they acted on an inhibitory neurotransmitter receptor called the GABA receptor. They were great drugs as sedatives for surgery, anxiety, and epilepsy. The problem was: you take too much of it and it can kill you by itself.

Benzodiazepines also act on the GABA receptor, but this chemist found that it's sort of a self-limited effect. It only works up to a certain ceiling, no matter how much more of a dose that you give.

And that's part of the controversy, right?
Ultimately, midazolam doesn't produce a depth of anesthesia of the old barbiturates. The issue is that because the midazolam doesn't produce a complete anesthesia, the body can still have reflex reactions to pain.

If a person was properly sedated, would it make any difference whether the executioner used potassium chloride or potassium acetate?
It wouldn't make a difference, no, as long as they use the same number of milliequivalents.

Okay what about the second step—the paralysis—how is that achieved?
It's a neuromuscular blocking agent, which is actually based on South American hunting arrow poisons. They would use it to paralyze their prey, and we have since adopted that natural chemical and made changes to it, but it essentially works the same way.

It works on a receptor where your nerves touch your skeletal muscle. It blocks the muscle side of the synapse—the gap point—between the nerve and the muscle, causing paralysis at a high enough level. The ones used in lethal injection are pancuronium or vecuronium.

Thanks so much. Is there anything else you'd like to add?
It's horrible that we talk about these medical things being used to execute a person but I think the acetate versus chloride thing, for this purpose, is only complicated because of legal issues. And I guarantee that if any corrections institute wants to use potassium acetate to execute a prisoner, it's going to have to go through a whole painful, million-dollar legal process that I think will be just as prolonged as the midazolam debate.

This interview has been condensed and edited for clarity.