Rivalry Gone Awry
Want to know what upholstery has to do with seizures? What poison murdered children during the Kindergarten Wars? What toxin sends a shiver of fear down my own spine? 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 Rivalry Gone Awry. Want to know what upholstery has to do with seizures? What poison murdered children during the Kindergarten Wars? What toxin sends a shiver of fear down my own spine? Listen to find out!
The charge nurse calls you in to Room 5 stat. A 19-year-old male is seizing. His body is convulsing with generalized, tonic-clonic contractions making it difficult for the medics to transfer him to the ED stretcher. The nurses cut off his urine-soaked clothes, try to attach the monitor and place an IV. The medic says no prior medical history, including no history of seizures.
Want to know the vital signs? Me too, though they’re difficult to measure under these circumstances. The blood pressure cuff won’t register because his arm is jerking continuously, same as the oxygen saturation. The o2 sat is often low during seizures, so we routinely administer 100% oxygen via non-rebreather mask. His heart rate is fast at 130 beats per minute. A forehead temperature reads 101.2 F (38.4C).
The nurses can’t get an IV. Instead, you call for an intraosseous kit, or an IO line. This is a needle you drill through the bone into the bone marrow to place a catheter for vascular access. IOs can go in the arm, below the knee or into the sternum. Happy to report I’ve never drilled a needle into anyone’s sternum. With the IO in place, you give lorazepam, brand name Ativan, a benzodiazepine to stop the seizure.
Giving the medicine a minute to kick in, you ask the medics for more information. The patient lives in the dorm at the nearby University. His roommate called 911. Per the roommate, the patient is otherwise healthy and doesn’t take any medicines. Having a first seizure in your teens or twenties isn’t uncommon and new onset seizures are a routine occurrence in the ER. Most seizures stop on their own after a minute or two.
You ask the medic the time of the call and check the clock. Twenty minutes ago. Meaning, this isn’t just a seizure, it’s status epilepticus, the medical term for seizures that won’t stop. The official definition of status is a seizure lasting for longer than 5 minutes, or more than 1 seizure in 5 minutes without a return to normal mental status in between. This definition is relatively new, in the past it was defined as a seizure lasting for more than 30 minutes. Why did the experts reduce the time? Because of the clear relationship between the duration of the seizure and morbidity and mortality, including brain damage.
I’m sure you’d like to have a lot more information, as would I, but our focus needs to be on stopping the seizure rather than taking a history. The most important intervention at this moment is aggressive treatment, so you order another dose of lorazepam and fosphenytoin a different antiepileptic.
Question number 1. What blood test is most important right now?
A. Sodium
B. Potassium
C. Platelets
D. Glucose
Answer: D. A blood glucose. If you said sodium, you aren’t wrong, it is important as both low and high sodium can cause seizures. However, we can do a fingerstick to get the blood sugar and fix it immediately if it’s low. The medic says they checked a fingerstick enroute and it was 100 mg/dL (5.6mmol/L) normal.
The patient’s still seizing. You check the clock, thirty minutes since onset. His risk of brain damage is increasing with every minute. There are a number of different algorithms for treating status epilepticus, the bottom line, it doesn’t matter which antiepileptic you use, it only matters that the seizures stop. I’d add another drug, probably levetiracetam, brand name Keppra. This is also a good time to call neurology, though you know what they are going to say. More antiepileptics.
Question number 2. What is the next best step for this patient?
A. An EEG
B. a CAT scan of the brain
C. an MRI of the brain
D. Intubation
Answer: D. Intubation. Why you ask? Has he suddenly developed respiratory failure? No. The side effects of antiepileptics are sedation. He’s currently still breathing, but we are giving a ton of meds and about to give a lot more. It’ll prevent us from worrying he’ll lose his airway because he’s too sleepy to breathe. You call for rapid sequence intubation medicines, usually a sedative and a paralytic.
Neurology answers your page and recommends phenobarbital, a barbiturate, as the next line agent. The patient is still on the stretcher, with no movement. Has the seizure stopped? Probably not. He’s not moving because we’ve given a paralytic, but most likely his brain is still seizing. Neuro sends a tech down to do continuous EEG monitoring to determine if the brain is still exhibiting seizure activity.
You’re about to call the ICU to get the patient upstairs when medics arrive with another patient. Also 19, also having seizures, also with no prior history. They mention this patient's roommate was also just taken to the emergency department for seizures. You ask if they picked him up from the University dorm. They did.
Uh oh.
I’d do the same thing for the second patient as we did for the first. Check a blood sugar, place an IV and start with a dose of lorazepam. You exhale a huge breath when this seizure stops with the first dose. The patient opens his eyes, but is very groggy and unable to answer questions. This is a normal occurrence called the postictal phase, occurring after afterwards, generally lasting for minutes to hours.
In the meantime, you jump to a pretty safe conclusion, your two patients are roommates. The addresses in the charts confirm your suspicion. Two patients from the same dorm room with the same symptoms? What’s happening here?
The first thing that comes to my mind with multiple ill patients, especially with neurological symptoms, is carbon monoxide poisoning. It's extremely common, very serious, and easy to miss. Do our patients have carbon monoxide poisoning? They certainly could. However, the medics says the other students in the dorm were hanging out of their rooms watching and crowding the hallway, so unlikely. The whole dorm, or at least most of it, would also be symptomatic. I’d send a CO level, because it's quick and easy to test for, but I don’t think it will be positive.
I also don’t think they both suddenly developed epilepsy or some other neurologic disease at the same time, so let’s move on to poisons causing seizures. There are approximately a million things on this list. As I've mentioned before, the endgame of many toxins is seizure coma death, but the list of toxins causing true status epilepticus is relatively short.
The differential diagnosis includes diphenhydramine or Benadryl, theophylline, chloroquine, bupropion, isoniazid, insulin, and things that increase or decrease sodium. It’s unlikely they both overdosed on the same medicine at the same time, so I’d cross those off. We can exclude insulin as their blood glucose is normal.
Ecstasy can cause hyponatremia, low sodium, and seizures. Maybe they both took ecstasy, sure, but it’s still unlikely they’d both have seizures as it’s not a common side effect. The labs from the first patient come back with a normal sodium ruling out those concerns.
Water hemlock, not to be confused with the poison hemlock that killed Socrates, can cause status epilepticus. Foragers confuse it for wild carrots. Were these students in the woods and accidently ate hemlock? Maybe, though this is an urban environment.
I love camphor for this. I’ve taken care of a lot of children with seizures after eating it. Camphor is in Vick’s Vapor rub, though usually in low concentrations. People use more concentrated blocks around the house to repel cockroaches and mosquitos. Some kids ingest it, developing toxicity and it can cause status, but unlikely two adults decided on this course of action.
After an hour, the post-ictal patient is back to baseline and able to answer questions. He confirms no prior medical problems and he doesn’t take any meds. Same as the first patient. They haven’t been foraging or eating camphor blocks. They were eating Chinese food when this started. I can’t tell you how many patients attribute their problems, even those that couldn’t possibly be related, to eating Chinese food. I’m already skeptical before he starts this story. He says our first patient was eating a Chinese dish given to him by a fellow Chinese student. Patient number 1 in turn offered some to patient number 2. Patient 2 took one bite, then dropped the dish on the floor lunging to help when his roommate started seizing.
This history triggers a thought. You tell the patient the plan is to monitor him closely under observation. You’re no longer skeptical about the Chinese food as the source of the illness. The thought of this toxin sends shivers of fear down my spine. You open the original patient’s chart. Neurology notes ongoing seizure activity on the EEG. The ICU team has given just about every antiepileptic in the hospital.
Question 3. Which of the following toxins causes status epilepticus?
A. Tetramine
B. Digoxin
C. Botulism
D. Tetrodotoxin
Answer: A. Tetramine, a cage convulsant. Cage convulsants are pretty much as terrifying as they sound. The name comes from their chemical structure in the shape of a cage. Picrotoxin is another cage convulsant, found in the fish berry, so named because fisherman would throw it into water stunning and killing fish. I guess making fishing a lot easier.
Tetramine is typically used as a rodenticide, a rat poison. It was accidently discovered in Germany in 1949. Upholstery workers developed headaches, vomiting, neurologic problems, psychiatric problems and seizures. They were working with rayon impregnated with sulfamide and formaldehyde to make it fire resistant. These chemicals reacted with each other, forming tetramine gas which poisoned the workers. Occupational history, especially since the industrial revolution, is really a minefield of toxins. It was eventually sold as a rodenticide.
How does tetramine cause status epilepticus? It binds to GABA channels in the brain. If you remember, GABA is an inhibitory neurotransmitter. So if you inhibit the inhibitor, you get unopposed excitation, meaning nonstop seizures. Severe poisoning is lethal without medical care.
Most of what we know about tetramine toxicity comes from China. There was an absolute epidemic of poisonings in the 1990s and 2000s. At one point in time, tetramine was listed by the WHO as one of the top 10 leading causes of death in Chinese people aged 5-29. Can you even imagine? A paper published in 2003 reviewing tetramine toxicity in China lists 35 separate incidents of tetramine poisoning.
It wasn’t even legal there during this period, having been banned in 1984, but it was readily available, especially in rural areas. Why? It’s cheap, easy to manufacture and works quickly. It’s sold under many names Dushuqiang is one, meaning very strong rat poison. Other names translate as “takes three little steps and keels over”, and “sniff and die quickly”. Three little steps must have a strong appeal to buyers of rat poison. Tres Pacitos, or three little steps in Spanish is the name of a different compound also used as a rodenticide. Listen to the Three Little Steps episode for more on that.
The poisonings in China were terribly tragic, but compelling, and caught the attention of news media worldwide. For example in 2002, a shop owner poisoned his rival shop owner’s food with tetramine, killing 42, and sickening 300. He was executed for murder. The same year, students fell ill from cafeteria food. An angry student wanted to poison his teacher, but instead poisoned his classmates. An episode called the kindergarten wars horribly ended in tetramine poisoning when an owner poisoned and killed several children at a rival kindergarten.
Tetramine is a white powder, colorless, odorless and tasteless. Poisonings have occurred via rice, yoghurt, water, porridge and scallion pancakes.
Not just acutely, tetramine is very persistent in the environment, lasting more than six weeks in water. Just how long it lasts was demonstrated after 12 family members became ill. They used an old grain depot site to plant a garden. After they became sick, tetramine was found in the soil of their garden. Tetramine had been stored in this location 10 years prior in the grain depot. The soil, and the vegetables from the garden, contained tetramine.
What about our patients. How do we know if tetramine is really what’s poisoning them? We don’t. In reality, we have to go on symptoms and clinical judgement. You can’t just order a tetramine test, you’d have to find a specialty lab to do it. I love the suggestion from one study to have a high level of suspicion for tetramine toxicity in patients who present with seizures and die within a short time.
How do we treat poisoning? Good question. Unfortunately, there are no good answers. Information is conflicting. Certainly, antiepileptics as we’ve discussed. All toxicologists would love to recommend GI decontamination to remove some tetramine, but a big issue is the speed with which it works. Onset of toxicity can develop within 30 minutes of exposure. Gastric lavage, or pumping the stomach may help, but hasn’t been shown to reduce mortality. Animal studies show charcoal binds tetramine, but giving charcoal to someone having seizures is contraindicated, due to the risk of aspiration.
Tetramine may be removed by dialysis, though efficacity and which particular modality is best are not clear. A vitamin, B6 or pyridoxine, might help. B6 is the antidotes for seizures caused by isoniazid, a TB drug. DMPS, a chelator, not approved for use in the US but available in Europe, is another potential treatment option.
Back to our patients. The second patient is fine and has no other seizures, thanks to taking only one bite of the poisoned food. The first patient eventually stops seizing, but sadly suffers permanent neurological damage. He won’t be able to return to the university and may never be able to walk again. Police investigate and find tetramine in the Chinese food. The source is traced to the fellow student who prepared the dish. Tetramine was found in hidden in his dorm room. The students were competitors, vying to graduate first in the class. The perpetrator planned to eliminate his competition. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.
As far as I know, tetramine was never legal in the US. There is only one case of tetramine toxicity reported here, in New York City. A 15-month-old-girl became poisoned after playing with illegally imported tetramine powder. She developed refractory seizures, though she survived, but with persistent neurologic deficits. One study followed up 350 poisoned patients. Half reported persistent seizures, six reported continued neurological problems. That study is from China, as is so much of our information.
We know thousands were poisoned and hundreds died. Given the lack of transparency of the Chinese government, those numbers could be much higher. The negative publicity led the government to cracked down on tetramine, going so far as to threaten to execute those buying and selling the poison. On a positive note, there have been fewer poisonings since.
This brings us to the last question in today’s podcast, which is a bit of a trick question. We toxicologists always promote the use of generic names, rather than brand names, to prevent confusion. For example, ibuprofen in the US is sold under many brand names including Motrin and Advil. Acetaminophen in the US is brand name Tylenol, but Paracetamol in other countries. Similarly, chemists don’t like common names, but advocate for use of the real chemical names, even if it’s a tongue twister.
This question is the reason why. When I first heard about tetramine as a fellow at the poison center, I did some research and was shocked to read it occurs organically, in nature. I became further confused when the symptoms of toxicity were the opposite, weakness and paralysis, rather than seizures. Finally, I realized the problem. Common names. Tetramine the rodenticide, the compound we’ve been discussing, is Tetra methylene disulfo teramine. It is not found in nature, but manufactured. The compound found in nature is tetramethylammonium. Both have, unfortunately, been shortened to the common name tetramine, despite being totally different substances. Last question. Where is naturally occurring tetramine found?
A. Octopuses
B. Sea snails
C. Yew trees
D. Poiosn hemlock
Post your answers on our Twitter and Instagram feeds both @pickpoison1. Follow and you’ll see the answer when I post it. 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. Transcripts are available on the website.
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.