The New Guy
Want to know what category of poisons is named the new guy in Russian? How a man dropped dead in minutes of a potent toxin applied by people wearing no PPE, without the poisoners suffering any symptoms? And what’s the antidote to these poisons? Listen to find out!
This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patients survive this podcast? It’s up to you and the choices you make. Our episode today is called The New Guy.
Want to know what category of poisons is named the new guy in Russian? How a man dropped dead in minutes of a potent toxin applied by people wearing no PPE, without the poisoners suffering any symptoms? And what’s the antidote to these poisons? Then stay tuned!
Thanks for your patience. This episode was delayed due to some much needed vacation time. I’m happy to report no poisonings occurred, unlike our fictional vacation episode a few weeks ago. Today’s podcast could be considered the second half of the last episode, number 8, Three Little Steps. I strongly encourage listening to that one, if you haven’t already, before proceeding here as this contains spoilers. To avoid repetition, many of the concepts I’ll touch on today are discussed in more detail there. If you want to go back, now’s your chance. If you’re ready, let’s go.
This case starts in the emergency department in Washington DC, near the Dulles International Airport. Medics call ahead with an advance notification giving a heads up about a very sick patient who collapsed in the airport. When they arrive, the patient is barely conscious. A single glance at his grey skin and shallow breathing tells you he’s deathly ill.
The man opens his eyes, groans, and says don’t let me die before he loses consciousness completely. The hair stands up on the back of your neck. Anxiety and panic attacks aside, people know when they are dying and this is no panic attack.
The medics tell you what they know. Bystanders said the man stumbled around for a few minutes, then fell to the ground. They checked his vitals, noting a low heart rate, low blood pressure, and a low oxygen saturation. After applying oxygen, they administered 2 mgs of atropine to improve his heart rate, but it didn’t respond to the medicine.
Indeed, the vital signs on your monitor are the same. The patient’s heart rate is in the 30s. His blood pressure is 80/40, and his oxygen saturation is 85% despite 100% oxygen via the mask applied by the medics. The patient is dripping with sweat. The oxygen mask keeps slipping down because he’s drooling so much. In addition, tears and sweat are rolling down his face. His breathing is labored. He’s audibly wheezing and when you listen to his lungs with your stethoscope, you also hear crackles. Vomit cakes his chest. The nurse cutting off his pants says, “Code Brown alert.” Stool and urine saturate his clothing.
If you listened to the last episode, this is a pop quiz. You should recognize this toxidrome. Quick hint, a toxidrome is a classic constellation of symptoms indicating a category of poisons.
Question number one. What toxidrome does this patient have?
A. an opioid toxidrome
B. a cholinergic toxidrome
C. an anticholinergic toxidrome
D. a sympathomimetic toxidrome
Answer B. A cholinergic toxidrome.
These are the classic symptoms medical students use the pneumonic SLUDGE to remember. He has them all. S for salivation. L for lacrimation, the tears streaming down his face. U for urination, D for defecation or diarrhea. And E is for emesis, or vomiting. The second half of the cholinergic toxidrome? The killer Bs. Bradycardia, bronchoconstriction or bronchospasm, and bronchorrhea. The symptoms of the cholinergic toxidrome that will kill the patient. The man is wheezing indicating bronchospasm, like asthma or COPD. We hear crackles in his lungs, the sound of fluid collecting there. And his oxygen levels are low, indicating the severity of these problems. His heart rate is also low.
We better do something fast before he collapses and dies. What’s the antidote for the cholinergic toxidrome? Again, if you listened to the last episode, you already know the answer. Atropine. The drug is a strong anticholinergic agent, working to reverse the effects of a cholinergic poison.
But wait a minute. The medics said they gave atropine and it didn’t help. Do we have the wrong diagnosis?
Question two. True or false. This patient can’t have cholinergic poisoning if atropine, the antidote, isn’t helping.
A true
B. False
Answer False. If you said true and treated him for something else— your patient didn’t survive this podcast!
The medics administered atropine at the standard dose for bradycardia or slow heart rate. We usually give 1 to 2 mg because this is enough to help the most common etiologies, those related to heart disease and conduction delays. Basically, patients who need pacemakers. A milligram or two is usually enough for treatment without causing side effects and buying time for a more definitive intervention.
We have to consider atropine’s lack of effect in this case, as it could indicate the wrong diagnosis. However cholinergic toxicity is often a clinical diagnosis given the limitations of lab testing and this patient’s symptoms are classic. Why then is atropine not helping? Because we haven’t given enough. Very large doses are typically required to reverse cholinergic toxicity. Per the bystanders, this man had a sudden collapse, meaning he was exposed to a very potent cholinergic toxin. It’s not the wrong diagnosis. It’s the wrong dose.
Enough talking, let’s get to work. Our patient needs large doses of atropine and he needs intubation and mechanical ventilation. You can do these things in either order depending on your assessment of his airway. If I thought atropine might keep him from needing a ventilator, I’d start there. This patient doesn’t look well and doesn’t have in intact airway. No matter what happens, he’s going to need airway protection, so I’d do that first. Then I’d start a doubling regimen of atropine. The medics said 2mg didn’t work, so I’d give 4mg and keep doubling every 10 minutes until we achieve atropinization. I’d also start the second antidote for cholinergic toxicity, an oxime, in the US pralidoxime or 2-PAM.
A quick review, cholinergic poisons work by blocking the enzyme responsible for breaking down the neurotransmitter acetylcholine. When acetylcholine builds up, there’s excessive stimulation of the parasympathetic system, the feed and breed, or rest and digest part of your body. The opposite of the sympathetic nervous system’s flight or fight response. The causes of cholinergic poisoning include medications, mushrooms, pesticides, and chemical weapons. Medications cause cholinergic side effects but almost never severe poisoning. I doubt that our patient consumed a poisonous mushroom at the airport. He could’ve been exposed to a pesticide or chemical weapon. However, we don’t have any other patients coming in from the airport. So if someone inadvertently spread pesticides around or intentionally released a chemical weapon, where are all the other patients?
Something doesn’t add up, but we can’t solve everything at once. Let's focus on what we can do, titrating the atropine to the right dose.
You talk to the nurse to adjust the drip. As you discuss the ventilator settings with the respiratory therapist, a person brushes past the curtains and enters the room, presumably a friend or family member. You turn to speak to them, in the hopes of obtaining more information about what happened. The visitor holds up his phone, pointed at the patient. He’s recording video. A clear violation of the patients right to privacy since an intubated, unconscious person obviously hasn’t given consent.
You spin around so you’re in front of the phone, blocking his view and put your hand over the camera. You call for security. They make him delete the video before escorting him out. As the doors open in front of them, you glimpse a chaotic scene in the ER waiting room. Not the usual tableau of pain and suffering, with patients draped over chairs, or leaning against family members. Instead, there’s two security guards attempting to keep a phalanx of cameramen and journalists at bay. At the hiss of the doors, attention turns to you in your white coat. Questions are shouted, cameras flash in your face.
You have no idea what’s going on, but also no time for this. Your patient is sick and needs your attention. All of your other patients, who also need your attention, have been waiting while you resuscitated this very sick person. Maybe the man is a celebrity. Of course, this is DC, so a politician more likely. From his name a Russian politician, maybe?
The unit clerk looks up from his phone and says, “That dude poisoned?” You raise an eyebrow. Nothing that happens in the ER is secret from the unit clerk. But they don’t usually ask about patient’s diagnoses. They’re concerned with demographics and checking patients in and out. He turns his phone so you can read the news headline. ‘Russian journalist and dissident poisoned?’
Well. This is a real code brown.
Just what you need. Caring for a critically ill patient and juggling a bunch of other patients? Hard. Doing that in the middle of a touchy political situation with a media circus? Impossible. Nothing like a bunch of nonmedical problems to distract you from your job.
As soon as you turn back to the vent settings, your phone starts ringing off the hook. The ED chairman demands to know exactly what happened. The ICU chairman wants to hear from you directly. Then the chairman of medicine, the chief medical officer, the CEO and someone from the Board of Directors calls. Someone with a heavy Russian accent calls saying they’re the ambassador, asking for a status update. When you stop answering your phone, the clerk keeps waving you over and telling you to pick up landlines. You tell all of them you’re too busy taking care of your patients to talk. This holds them at bay, for a whole five minutes until they all start calling again.
Your mission now? Get this patient up to the ICU as soon as possible before these distractions paralyze the ER and harm the other patients. You won’t personally be off the hook, since the ICU will consult you for a toxicology consultation. But at least getting him upstairs will allow the rest of the ER to function.
You double the atropine dose a few more times until you're satisfied you’ve achieved atropinization. His heart rate comes up to the 60s. His secretions dry up. He stops wheezing.
You breathe a huge sigh of relief when the ICU bed is finally ready and he’s transported upstairs. You turn your attention back to the other patients. You finally have a minute to go to the bathroom. Or so you think. The charge nurse intercepts you before you get there. Two more patients from the airport on the way.
Uh oh.
Should we activate a mass casualty? Maybe a chemical weapon was released at the airport. Though if that’s the case, this is an awfully slow progression of events. It’s been at least two hours since our patient collapsed. The nurse says these two are coming in with the police— not medics. Minimal symptoms, she says.
Two women arrived, handcuffed, each surrounded by a small army of police and men in dark suits. Neither woman looks like a dangerous criminal. Neither one looks sick. One officer says these two women poisoned your patient and are under arrest. They’re here for medical clearance before going to jail. You ask what happened and he starts off on a long story about immigration, reality TV shows, and guilty behavior. You stop him. You only need the medical information, not the legal details. No point in developing prejudice against these women and what they might or might not have done. You're the doctor, not the judge or jury.
Instead, you interview the first patient, she reports an episode of vomiting in the car ride to the ER but currently denies symptoms and has no other medical complaints. Her heart rate is sixty-three, on the low side but still normal, the rest of her vitals are normal. At 90 pounds, she exhibits the thin twitchiness and unhealthy dentition of a meth user. You tell the nurse to hook her up to the monitor for a two-hour observation period to watch for the development of symptoms.
The second patient also has a petite frame, though she looks healthy. She denies any symptoms whatsoever. Your plan for her is the same course of observation.
What exactly is going on here? If law enforcement is right, how did these women poison the patient without getting sick? The patient collapsed, nearly dying within fifteen minutes per bystander report. He is a large heavily muscled man, and weighs more than both women put together. How could they possibly have poisoned him with a potent toxin, remaining unaffected themselves?
A gas mask? Or hazmat suit? You’d hardly be unobtrusive at the Dulles Airport dressed like that, at least not since 2020. You ask if anyone else at the airport is ill, the officers say everyone is fine. The police say the two women ran up to the patient, then ran away. He collapsed shortly thereafter. You ask to see the security footage, They tell you it’s classified. Fortunately, the unit clerk has already found it online so you can review what happened in detail.
I’m going to pause here on the fictional case and instead discuss the real case where a similar sequence of events happened. Instead of Dulles, it was an airport in Malaysia. The security footage is grainy, but still shocking. It shows a man in the airport walking around, looking perfectly healthy. A woman runs up, rubs something on his face, and runs away. A second woman does the same. Almost immediately the man stumbles around and collapses shortly thereafter. The man was Kim Jong-nam, exiled half-brother of North Korean dictator, Kim Jong Un. Kim Jong-nam was assassinated, dying 15 to 20 minutes later, on the way to the hospital. This, despite the fact that he had twelve doses of atropine in his suitcase.
Question 3. Swabs of Kim Jong-nam’s face and eyes confirmed his death was caused by?
A. VX
B. Sarin
C. An organophosphate pesticide
D. Hydrogen sulfide
Answer: A VX.
What wasn’t surprising about this case was that he died of cholinergic toxicity. His symptoms on the security footage and those described by bystanders, were pretty classic.
The surprising part was the two women, also clearly seen on the security footage, and later arrested by the authorities, were completely fine. The video shows them wearing regular clothes and no PPE. Not even gloves. How did these two women kill him with a toxin so potent he couldn’t get to the atropine in his bag, so potent he died within 15 minutes, while they themselves, without even gloves, were perfectly fine? VX can be in gas, powder or liquid form. All are lethal. Here? The VX was probably in binary form.
What’s a binary toxin? Binary poisons are when two nonlethal, or minimally toxic, precursors are combined to form a poison. There are many types of binary poisons. The starting compounds can be something as benign as household cleaning products. Remember the detergent suicides? In 2008, hundreds of people in Japan, then around the world, committed suicide via this method. Cleaning products were combined in a small space, like a car. The subsequent chemical reaction released deadly hydrogen sulfide gas. In this case the hydrogen sulfide gas was a binary agent, having been produced by two otherwise non-toxic household cleaners.
In the case of VX, the binary form is sometimes called VX2. There are actually several methods to create VX2 from non-toxic precursors. The hypothesis in Kim Jong-nam’s death is that each woman had one of the nontoxic precursors on her hand, so each was safe. Kim Jong-nam, however, was not safe when the two compounds formed lethal VX on his face. Death from VX occurs in minutes to hours depending on the dose and the route of exposure. 10 mg if ingested, a mere two teaspoons, is enough to kill someone.
Another category of binary agents, called novichok agents, is extremely concerning. Novichok means newcomer, or new guy, in Russian. They were the focus of research in the USSR and Russia from the 1970s to the 1990s. There are at least five different agents, and probably many more. They are reportedly 100 to 1000 times more potent than VX, the most potent traditional nerve agent. Most work like VX and organophosphates causing cholinergic toxicity. They undoubtedly have other effects, but other than a few limited reports, no one really knows because the formulas are state secrets. So secret, the Russian government denied their existence until 2018.
What happened in 2018? Confirmed novichok poisonings. The incidents were very dramatic, capturing the attention of the media and the public for months, and forced the Russians to acknowledge novichok agents existed. It was the poisoning of double agent spy Sergei Skripal and his daughter Yulia in the UK. Sergei was ex-GRU, a Soviet military intelligence officer, convicted and imprisoned in Russia for being a double agent and passing information to the UK government. After his release during a spy exchange program, he resided in England.
Sergei and Yulia collapsed on a park bench after dining at a restaurant. Passing in and out of consciousness, they were taken to a nearby hospital and initially treated for opioid poisoning. The next morning, doctors recognized a cholinergic toxidrome, prompting an investigation. Both Sergei and Yulia were severely poisoned and in critical condition for weeks. Fortunately, both survived.
I frequently mention difficulties with toxicology testing, this case really illustrates them, so let me highlight the timeline. The Skripals fell ill on March 3. The investigation started the following day, March 4. It wasn’t until March 12 the British announced testing confirmed the poison was indeed a novichok agent, as had been suspected. Almost two weeks to get an answer, in an extremely high profile, politically sensitive case, with no doubt unlimited resources. On March 28, the source of the poison was identified as the Skripal’s front door handle.
In the meantime, millions of pounds were spent identifying the source and decontaminating locations the Skripals had been as well as law enforcement equipment that potentially had been in contact with the toxin. The concern for cross-contamination and environmental pollution didn’t play out, with one tragic exception I’ll get to in a minute, in the Skripal case. This is in sharp contrast to a different case with a different poison, that of Alexander Litvinenko who was poisoned by radioactive polonium. Different patient, different poison, same government. You might be noticing a trend. More on polonium in a future episode. My point here is, just imagine how long testing would take for a regular patient, under regular circumstances.
The Russians, and other bad actors, don’t have any trouble with access to lethal poisons. Why then did they bother spending 30 years developing novichok agents? Hazarding a guess, they’re probably still testing and developing them. The appeal of Novichok agents is for several reasons. Certainly, you know treaties have been signed to control the supply and stockpiles of chemical weapons. Precursors to manufacturing them are tightly regulated and monitored in a further attempt to keep them in check.
Remember the last time you went to the pharmacy to get pseudoephedrine for a cold? It was probably locked up or behind the counter. Depending on the state you live in, you might’ve had to show your ID and you might’ve been limited to purchasing just a few boxes. This was an attempt to control one of the common precursors in methamphetamine synthesis. At one point, meth cooks required boxes and boxes of pseudoephedrine to make meth. Once access to pseudoephedrine was regulated, the cooks pivoted, developing different methods to synthesize it. Novichok agents are a similar, but much more sophisticated way, to get around chemical weapons restrictions and regulations.
First, they’re designed to be undetectable to typical chemical weapons detection equipment. Second, they are much safer to handle. The case of Kim Jong-nam dramatically illustrates this aspect. Third, and probably most importantly, they circumvent the chemical weapons convention’s list of controlled precursors. In fact, one of the precursors to VX2 is isopropanol— rubbing alcohol. Nobody wants to carry VX on a plane and risk exposing themselves. Transporting benign precursors like rubbing alcohol? No problem.
The Skripals survived. One woman, however, was not so lucky. On June 30, 2018, almost 4 months after the father and daughter were poisoned, a woman in Amesbury, England collapsed. Dawn Sturgess sprayed perfume on her wrist, collapsed within minutes, and died in the hospital several days later. Her boyfriend Charlie Rowley, also became ill, but he survived. He’d found the perfume bottle in a dumpster and given it to her as a gift. The subsequent investigation confirmed the perfume bottle contained the same Novichok agent used to poison the Skripals. Amesbury is about 7 miles away from their house. The generally accepted belief is the poison was disguised as perfume, used to poison the Skripals, then disposed of in the dumpster where Rowley found it.
Novichok agents are oily substances and because of this, persist in the environment. They can be removed with soap and water but if not washed off, remain where they are placed. Thus the UK government discovered the residue on the door handle weeks later. A poisoning in Moscow highlights this quality. In 1995, a Russian businessmen died. One month later, his secretary developed similar symptoms and also died. It’s believed the novichok was on his telephone and his secretary died using the phone after his death.
Another very high-profile case implicating a novichok agent is the poisoning of Aleksei Navalny. An outspoken critic of Putin, he fell ill on his jet with a cholinergic poisoning. He was transferred from a Russian hospital to a German one. The Germans confirmed he was ill due to a novichok agent. After his recovery, Navalny published a recorded a conversation. He impersonated a Russian security official and spoke with a chemical weapons expert involved in his poisoning.
Question #4. Where was the novichok agent used to poison Navalny placed?
A. Tea
B. Muffin
C. The desk in his private jet
D. His underwear
Answer: D. The man reported the novichok was placed into Navalny’s underwear.
Let’s get back to our patient. You do your best to stay focused, working with the ICU team to manage his medical problems. The authorities establish a security perimeter in the ICU to keep the patient and staff safe. The media circus worsens as more information comes to light. The man is a Russian dissident, a journalist, who opposes Putin’s authoritarian regime. Testing confirms he was poisoned with VX. Fortunately, our patient is weaned from the ventilator after several weeks in the ICU and recovers. He doesn’t suffer any long-term consequences as some exposed to novichok agents have.
This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings that have occurred. I’m certain this is the not the last we’ll hear about novichok agents. Given the ease with which they can be concealed and the damage they cause, it’s doubtful their popularity in clandestine poisoning will decrease.
Nerve agents have been in existence since World War II and in fact their classification reflects this. They are split into two categories, the G series and the V series. G because these agents were first synthesized by the Germans. Tabun (GA), Sarin (GB), and soman (GD) are in the G series. VX is in the V series. The German’s never used the nerve agents they developed on Allied troops. Sarin you may remember was used by a cult in the Tokyo subway poisonings and horrifically to kill civilians in the Syrian Civil War in 2013. Despite attempts to control stockpiles and access to chemical weapons, they remain an omnipresent threat.
On to a lighter topic and today’s Pop Culture Consult. Also, our last question.
In the movie Goldfinger what toxin is used to poison the water supply at Fort Knox?
A. VX
B. Sarin (GB)
C. A novichok agent
D. Morphine
Post your answers on our Twitter feed @pickpoison1. I’ll post the answer in the next 24 hours. Remember, never try anything on this podcast at home or anywhere else.
Finally, thanks for your attention. I hope you enjoyed listening as much as I enjoyed making the podcast. It helps if you subscribe, leave reviews and/or tell your friends.
All the episodes are available on our website pickpoison.com, Apple, Spotify or any other location where podcasts are available. Our Facebook and Instagram pages are both @pickpoison1. Additional sources like references and photos are available on the website along with transcripts.
While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Thank you. Until next time, take care and stay safe.