of Bomb Shelters and belladonna

When I was a teenager in the sixties, some of my friends were lucky enough to have fallout shelters; a perfect make-out spot right in their own basement! Somehow, the government had people convinced that, in the event of nuclear war, you could bundle the family down into a prepared corner of the basement, eat dried beans and look at each other in an 8 by 10 foot room for a few years until the radiation all clear was sounded by whoever-was-left-that-might-know, and then emerge to defend the American Way. As late as 1969, my high school health class consisted of pithy lessons on what was safe to eat after the war (all I remember is that beef with green stuff on it is ok if you trim off the green...) and the effects of Beta and gamma radiation. Well, Physicians for Social Responsibility finally named the lie of conventional survivability (THE LIVING WILL ENVY THE DEAD). So did books like "A Canticle For Leibowitz" and movies like “The Day After".

As near as I can figure, the government spends half their time scaring us witless, and the other half telling us that if we do as instructed we'll all be just fine. That routine is timeless; it’s like ding-dong-ditch. That's why we get to take off our shoes at the airport; it's the antidote for color-code-threat-level induced anxiety. But this post isn’t about commercial aviation or government manipulation of public mood; it’s about nerve gas.

Part I. A Brief Primer

Nerves talk to each other and muscles with many signaling chemicals, chief among them acetylcholine, (Ach for short). The signaling nerve releases Ach, which causes the "listening" cell on the receiving end to do its thing; contract (muscle) secrete snot (the lining of the nose), think (brain cell) etc. It's the chemical "On" switch. AcH is an ancient neurotransmitter, found in very primitive life forms, and different AcH receptor types have evolved over time. As you read this, stop for a moment and tap your finger on the table as fast as you can. Not only must AcH act quickly, it better go away pretty quickly too, or it’ll clog up the receptor sites at the listening (effector) cells; otherwise, you tap once, you’re stuck. Evolution provides; AcH gets almost instantly destroyed by acetylcholinesterase right at that receptor site; acetylcholinesterase is an enzyme that lives to eat AcH; It's the "off" switch.

Now, deactivate the acetylcholinesterase and you get... chaos. Blue screen crash. It’s the physiologic equivalent of an internet Denial of Service attack; AcH mobbing receptors which fail under the load. It's all "On" and no "Off."  Muscles spasm and go flaccid. Seizures, Diarrhea, salivation, Asthma. You die convulsing in your own effluvium. Not pretty.

Anesthesiologists make part of their living gently tweaking acetylcholine and its receptors. We use  very weak drugs that either block acetylcholinesterase or block the receptors for AcH ("competitive inhibition"). It’s a juggling act; the reward of doing it right is we get to control lots of patient physiology. It’s a little like being a pharmacologic puppetmaster. Very empowering. The price of doing it wrong is inconvenient. The drugs and doses are so weak, that unless the anesthesiologist is particularly inattentive, imbalances can be quickly rectified.  We use curare's descendants to intentionally paralyze muscles, and we reverse the effect after a while with neostigmine which mildly deactivates acetylcholinesterase and thereby pushes up AcH levels at that same receptor, effectively shouting the "On" signal past the blocker. Atropine does nothing at the muscle receptor, but blocks gut and heart AcH receptors so that the AcH signal doesn't pass through.

Neostigmine is weak. Organophosphate insecticides (malathion, others) do the same thing as neostigmine, only they are eight hundred pound gorillas. They work as insecticides because insects have AcH receptors, just like we do. (Ancient, remember?) You get a decent whiff of this stuff (or a little on your skin) and you get all the above symptoms pretty quick. If you're lucky, they rush you to hospital (assuming that the people trying to save you don't pick up a dose through skin contact and join you in your throes) where the ER staff washes you off and titrates doses of receptor blockers (atropine), and administers anti seizure medications (valium and its cousins). You will also be intubated and ventilated, since there is no suitable antidote for the muscle receptors.  If they get it right and early, you might live, but you might have permanent damage to your receptors or brain. It's not like "The Rock" where Nicolas Cage stabs himself in the heart with antidote and saves San Francisco. (also, nerve gas doesn't cause your flesh to melt; that was just to sell tickets) Organophosphate insecticides are the sad method of choice for suicide amongst debt-crushed Indian farmers.

Nerve gas does the same thing, only it's even more potent... It's like human insecticide. Israelis keep rolls of duct tape and plastic sheeting around in case of attack to seal off a room. This might work, I suppose, if you are lucky and fast, and have some air tanks to maintain positive pressure and an oxygen supply.

The military carries around atropine and pralidoxime injectors. (pralidoxime re-activates acetylcholinesterase, although doubts have been cast on its efficacy) I don't really know if this actually works; data on successful field resuscitation is scant; I'm not sure what they would do about seizures and paralysis.

Some nerve gas comes and goes fairly quickly in the environment; a week or so (sarin or GB). Some is oily and hangs around like a booby trap (VX) for weeks waiting for you to touch something and absorb it through your skin; a hellish chemical minefield. Notice how infantry now always wears gloves in combat field ops...

The truth is, it is hard to defend against this sort of thing.  The Academy of Science and Institute of Medicine have a most excellent review of nerve gas science online, if you're interested in more detail.

Although ER physicians will be first responders, I think it likely and appropriate that anesthesiologists participate in the response, since we are most familiar with the clinical manipulation of AcH receptor physiology and airways. Once in my career I have been in the position of taking care of a patient while I was protected only by a hospital provided gown, N95 mask and plastic visor in a situation where the responding fire rescue team felt the situation warranted full hazmat gear; that was a little scary (it turned out ok... so far).  That's my way of suggesting that you check out your hospitals' preparations for hazmat and virulent infection patients before you need the gear.

As the title suggests, I'm a a tad skeptical about all this. I'm not sure we're not just building fallout shelters here. But in the end, my anesthesia (and Boy Scout) nature gets the better of me, and I say "be prepared."  Intellectualization is a powerful emotional defense. I even have a roll of duct tape...

Comments

[Anon]

Members of the military have auto-injectors for diazepam or midazolam, as well as the standar atropine/2-PAM injector pack. Midazolam is being worked in as the replacement for diazepam. Servicemen and women in areas where risk of exposure is considered high are also maintained on a prophylactic dose of pyridostigmine bromide, so that the 2-PAM has sites to work upon.

Though it's been two years since I worked as a civilian researcher for the US Army, I believe SOP remains that any non-medical member is allowed to administer up to 2 anticonvulsant doses, 2 2-PAMs, and as many atropine injectors as they can find in case of suspected nerve agent exposure.

[mkeamy]

Thank you for your comment. I suspect that the military has more extensive experience on the outcomes and likely dosing requirements for nerve agent exposures. I am intrigued that pyridostigmine pretreatment is helpful, but I know from other contexts that they wouldn't do it if they didn't have data suggesting it works. I recall twenty+ years ago a study where half of combatants were given decadron and half were not pre-combat, in order to test the hypothesis that prohy steroids would improve combat survival (didn't, I was told) anyway, nerve gas treatment data is not easily forthcoming, I assume for obvious security reasons... Anyway, thanks for the comment