The Hazardous Holiday
What to know what poison is more potent than cyanide? Where it occurs in the natural world? And what famous explorer survived his exposure to it?
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. This episode is called the Hazardous Holiday. What to know what poison is more potent than cyanide? Where it occurs in the natural world? And what famous explorer survived his exposure to it? Then stay tuned!
Today we’re in Thailand on a trip with a group of friends. To combat jet lag, you napped for a few hours before meeting for dinner. A loud commotion in the hallway outside your room wakes you up. You look at the clock and realize you forgot to set your alarm clock and missed the meal, a mistake that may have saved your life.
The voices are those of your friends and traveling companions, two fellow ER doctors. Chris stumbles down the hallway, speaking in a slurred voice. Alice is steady on her feet and trying to help, but her petite frame isn’t up to the task of supporting his heavy weight. Chris lurches into the wall.
At first glance, he appears intoxicated with slurred speech, difficulty walking. You don’t need a toxicologist to tell when someone’s drunk. Alice is very concerned, not irritated or annoyed, but worried. A look you’ve seen on her face in the ER right before a patient has a life-threatening event like a cardiac arrest.
Before you can assist, Chris falls, hitting his head. He doesn’t get up. He lays on the ground, awake but not speaking with extremely large pupils. A list of grim possibilities races across your mind. Thailand is famous not only for beautiful beaches and delicious food, but also for sex tourism and drugs. You shake the thoughts out of your head, Chris wouldn’t expose himself to those risks.
Alice says they met up with a local, the friend of a friend, and were invited back to his house for dinner. During the meal they drank ya dong, the local alcoholic drink and consumed delicacies his wife cooked for dinner. Chris started to feel ill and after apologies to the host, they left to return to the hotel.
Alice says Chris had a few drinks, but not enough to account for the severity of his symptoms. You carry a pharmacy’s worth of meds in your suitcase first-aid kit, but nothing in there is going to fix this. Your friend doesn’t look good. You call the front desk for emergency help. Fortunately, this island has a hospital with the capacity to care for sick patients. The hotel sends a car for transport.
The reason for the trip is, ostensibly, an emergency medicine conference. The truth, a group of very tried ER doctors hoping for a week of rest and relaxation on a beautiful tropical island, with a dash of learning thrown in on the side. You and your friends are suffering from burnout, or it’s better name moral injury, just like all ER doctors these days. The antidote: a few days of sun, surf, good food and tropical drinks. A tour of the local ER, while potentially interesting, wasn’t on the itinerary.
On the way, you and Alice discuss what could’ve happened, same as you would on shift with a patient. Malaria is always a consideration in tropical locations and there’s plenty of malaria in Thailand, but it doesn’t cause a sudden collapse out of nowhere. Chris would’ve complained of fevers and muscle aches, and the symptoms would’ve develop over hours to days. Alice rattles off a list of exotic tropical diseases neither of you have ever treated, but you’re both in agreement that few of them would strike like this with no other symptoms.
Alice tells you the host joked he’d added lizard and snake to his homemade ya dong, the alcohol they were drinking, basically Thai moonshine. Any homebrewed alcohol can be dangerous. Methanol, a toxic alcohol, is created during the first part of the distillation process. If not properly removed, it causes blindness and death. Alice drank the alcohol herself and feels perfectly fine. While toxic alcohol poisoning is certainly a consideration, the symptoms develop over hours not immediately. Alice thinks he was joking about snakes, but wonders if he wasn’t.
Question number 1 in today’s interactive podcast. Ingesting (drinking) snake venom causes toxicity. True or False?
Answer: False. Snake venom is broken down—inactived-- in the stomach and therefore not likely to cause toxicity.
What about the food? Alice doesn’t know the names of the dishes, but they ate spicy soup, Barramundi fish curry, squid, and horseshoe crab roe. The food was delicious except for the horseshoe crab roe, eggs, which she describes as tasting like briny rubber and admits she discreetly spit it out into her napkin to avoid gagging. Chris and Alice hadn’t eaten horseshoe crab before, but it’s such a popular local delicacy it’s advertised on signs from the airport. Alice noticed Chris rubbing his face, then asked to use the bathroom with a look on his face suggesting gastrointestinal distress. Shortly after returning, he apologized said he wasn’t feeling well, might have gotten food poisoning from an earlier meal, and needed to leave. He had difficulty walking and once outside the house, complained of numbness and tingling in his face. Alice barely managed to get him into a tuk-tuk back to the hotel.
You have a suspicion about what happened just as you arrive at the hospital. Two people carry an unconscious man from another vehicle. Alice gasps.
“That’s our host!” she exclaims.
Uh oh.
Obviously, Chris and the dinner host will be taken care of by local physicians not you. In real life, I’d steel myself to watch from the sidelines rather than take charge of their care. Every ER doctor I know has a hard time sitting back and watching. But, this is a fictional case so, rather than sit on the sidelines, lets imagine we are taking care of these patients and making the decisions. This scenario could happen anywhere, more on that later.
You put aside your suspicions for the moment and focus on stabilizing the men first. The physical exam reveals the same findings in both. The monitor shows a slow heart rate and slow respiratory rates. They are both paralyzed, neither can move their arms or their legs and they can’t speak. Both have large pupils.
If you listened to other episodes, you know the first step for assessment of sick patients. The ABCs. Airway, breathing and circulation. Chris is breathing, his chest is moving, but barely moving, instead of rising and falling normally. His breathing is inadequate. The host isn’t doing much better and is drifting in and out of consciousness. Both are teetering on the verge of respiratory failure. Why? Have they suddenly developed lung disease? No.
There are two parts to breathing. Gas exchange in your lungs is the first– trading oxygen for carbon dioxide. Second is ventilation, the mechanical movement of air into the chest. The contraction of the diaphragm pulls air into the lungs and its expansion forces air out. The diaphragm is a muscle, small and critical, but just the same as the rest of the muscles in your body. Things that cause muscle paralysis kill you by paralyzing your diaphragm and halting your breathing.
You determine both men need to be intubated and hooked up to ventilators. After you finish, you’re confident they’re stable for now. But you don’t know what to do next. Rather than panicking—your friend is intubated in a foreign country suffering from a dangerous, but unknown illness—you calm yourself down and organize your thoughts to focus on the cause of this illness.
Common diseases causing paralysis are stokes, and intracranial hemorrhages—bleeding in the brain. Those typically cause symptoms on one side only. Spinal cord injuries cause symptoms on both sides. Did two people coincidentally develop spinal cord pathology at the same time? Not likely.
The medical term for their condition is flaccid paralysis. Flaccid here meaning muscles that can’t contract. If you were thinking of something else, try Episode 1, Love Hurts. Polio is a classic cause. They didn’t both develop polio in the last hour. Encephalitis can certainly cause paralysis but again, immediate onset is unlikely. As with malaria, we’d expect cold and flu symptoms, fever, headache,etc before suddenly becoming paralyzed. Electrolyte disturbances are possible like very low potassium or very high magnesium. Not likely in an otherwise healthy patient.
This is a toxicology podcast, so let’s talk about the toxicological causes of flaccid paralysis. If you listened to episode two, you know heavy metal poisoning causes both gastrointestinal symptoms as well as neurological symptoms. Chris got up during dinner to run to the bathroom. We’ll keep it on the list of potential diagnoses, but rapid onset like this is extremely unlikely with heavy metals. Snakes with neurotoxic venom cause paralysis, Thailand has plenty of poisonous snakes, again the history is lacking.
Botulism is a great thought in any case of flaccid paralysis. Paralysis can be ascending, starting at the feet and moving up, or descending, from the head moving down. Chris’ symptoms started in his face, so this is descending paralysis, the kind of paralysis botulism causes. Did the host serve some bad canned food? Probably not. Botulism toxicity occurs over days, not minutes. Alice said Chris and the host were perfectly fine at the beginning of dinner.
This brings us back to the red flag you noted as we arrived at the hospital. Question number 2. What is the potentially toxic item on the dinner menu?
A. Squid
B. Barramundi fish
C. Horseshoe crab roe
D. Thai chili peppers
Answer: C horseshoe crab roe
While there are octopuses poisonous to humans, more on this in a few minutes, I’m unaware of any squids causing toxicity to us. Barramundi is popular in Thai cuisine, often compared to sea bass. Fish and seafood obviously cause allergic reactions, they occasionally harbor disease-causing bacteria, but the fish didn’t poison our friends. Thai chili peppers are extremely spicey. Everybody knows what happens when you eat a hot pepper, pain not paralysis.
Horseshoe crabs do contain a very potent toxin, one that causes flaccid paralysis. Tetrodotoxin. Shouldn’t the host have known better? Why then is it eaten on this island and advertised as a delicacy? Great question. The answer is that some horseshoe crabs contain tetrodotoxin and some don’t. We’ll get back this, but first let’s talk about tetrodotoxin, what it is and what it does.
Question number 3. What organism or organisms contain tetrodotoxin?
A. Octopuses
B. Newts
C. Frogs
D. Worms
Answer: all of the above.
The most fascinating thing in my opinion about tetrodotoxin is where you find it. Amazingly, the same poison is found around the world in widely differing species both on land and in water. It’s in pufferfish, blue-ringed octopuses, newts, frogs and worms. You probably know pufferfish are toxic. I want to talk about this in more detail, since it’s the most common source of poisoning. Pufferfish can be eaten anywhere, its especially popular in Japan where it’s called fugu. Japanese chefs undergo years of training to learn how to prepare it safely without poisoning diners. They practice on hundreds of fish before they’re certified. In pufferfish, tetrodotoxin is concentrated in the liver, ovaries and testicles. Tetrodotoxin is more potent than cyanide. During training, chefs learn which parts to remove and how to do so without contaminating the rest of the meat.
People are still poisoned each year. Why? First, the preparation might go wrong. This is rare, but not impossible. Second, Some species of pufferfish contain tetrodotoxin, but others don’t. Fisherman have mistaken toxic species for nontoxic species safe to eat without special preparation. The last way is the most surprising, at least for me. If you can believe it, people sometimes intentionally eat the parts thrown away by the trained chefs, the organs with the highest concentrations of tetrodotoxin. We’ve previously talked about people eating testicles as an aphrodisiac. Also, some people apparently believe they have a special, homemade recipe to detoxify the fish. Kimo is the Japanese word for pufferfish liver. Tetrodotoxin is heat-stable, meaning cooking doesn’t change or destroy it. A number of people have been poisoned after eating homemade kimo.
If pufferfish without tetrodotoxin exist why aren’t those eaten instead of taking a chance on the preparation? People do eat them in many Asian countries. In some places like Japan, diners complain the farmed tetrodotoxin aren’t as tasty as the real fish. True? Or does the risk of death add to the taste?
I have to share a story with you about my own personal experience with pufferfish. I went with my husband to a fancy Japanese restaurant in New York. The waiter announced the daily special was fugu and husband ordered it because he’d always wanted to try it. The fish was served sashimi style, the thin, almost translucent, slices arranged in the shape of a chrysanthemum. Quick aside, is it a coincidence chrysanthemums are part of funeral arrangements in Japan? After he ate it, I asked if he had any numbness or tingling in his mouth, which sometimes occurs even with properly prepared fugu. He said no, no symptoms and we continued with the rest of the meal. I didn’t eat the fugu, not out of fear of poisoning, but because I don’t like fish.
About ten minutes later I got up to use the restroom. As soon as I stood, my husband said, “Where are you going?”
I answered, “The bathroom.”
He said, “You can’t leave.” I pointed to the door, not far from the table, a little confused as to why he’d object.
He said again, “You can’t leave me.”
I suddenly realized the problem and started dying of laughter. He was counting on me to be at the table in case he developed tetrodotoxin poisoning and was worried he might become paralyzed while I was in the bathroom. I’m happy to report he was fine while I was away from the table and suffered no side effects from the fugu except the mild separation anxiety.
So what is the treatment when something goes wrong and a patient is exposed to tetrodotoxin? Activated charcoal we’ve discussed before binds many substances and may be helpful, but only if it’s given within the first 30 to 60 minutes. Lab experiments show it binds the poison, but it hasn’t been shown to improve mortality in humans. In addition to arriving to the ER quickly, the patient has to be awake and alert. Charcoal damages the lungs if aspirated. Both men were too sleepy by the time they arrived at the hospital. A number of other treatments have been tried, none of them proven to work.
Bottom line -- intubation and treatment of respiratory failure along with supportive care is the best option. If a patient receives care before suffering respiratory failure, their expected outcome is good. The ventilator breathes for them until the toxin wears off. Long term effects are not expected.
Without intervention, tetrodotoxin is lethal. The Japanese report about 20 to 40 cases of toxicity per year with an estimated mortality rate of 6.8%. This reflects the utility of modern medical care, because in the past mortality rates were as high as 40 to 50%.
What does tetrodotoxin do? It’s a sodium channel blocker, meaning it binds to and inhibits sodium channels. In the body, this interferes with nerve conduction and muscle contraction, causing paralysis. As I said earlier, it kills you by paralyzing your diaphragm and causing respiratory failure.
There’s controversy surrounding the source of tetrodotoxin production in animals, whether it’s endogenous or exogenous with evidence for both. Endogenous, meaning fish and other species can produce the compound themselves. Exogenous production means tetrodotoxin is inside the fish, but produced by a different organism like bacteria. Vibrio and pseudomonas bacteria synthesize tetrodotoxin. Fish, and other marine life, acquire the toxin from bacteria in the water and from eating smaller organisms.
Not only the species, but where the animal lives can determine its toxicity, due to its diet. A snake’s diet determines the composition of its venom. Similarly, Pufferfish fed a tetrodotoxin free diet may lose toxicity while others fed a diet high in tetrodotoxin develop toxicity.
How do animals ingesting a deadly poison avoid dying themselves? They’ve developed interesting mechanisms to avoid toxicity. The first is an alteration in their own sodium channels, causing it to be resistant to tetrodotoxin. The second is a protein which binds to and inactivates tetrodotoxin.
The poison is concentrated in different areas in different species. In horseshoe crabs, it’s in the roe, or eggs, presumably to improve offspring survival. In pufferfish, it’s the liver and reproductive organs. In newts, its highest in the skin to repel predators.
The onset time is fast, occurring 15-60 minutes after ingestion. There’s a grading scale for severity. Grade one, is early symptoms and mild exposure with lip numbness and tingling. Grade 2 is numbness and tingling of the tongue with some mild incoordination and slurred speech. Grade 3 is flaccid paralysis, with mild respiratory failure. Aphonia, the inability to talk because of a paralyzed laryngeal nerve, along with fixed and dilated pupils. Grade 4 is severe respiratory failure causing hypoxia, low oxygen, a Low blood pressure and heart rate, and an unconscious mental status.
Back to our friends. Alice says the dinner host caught the horseshoe crabs himself. Like pufferfish some species have tetrodotoxin and others are safe to eat. In Thailand, mangrove horseshoe crab roe is poisonous, Indo-Pacific crabs are safe. Health advisories have been issued by the government in the past after deaths due to misidentification. The species can be differentiated by their tails. The bad news is the host cooked the wrong meal. The good news, the island has a hospital and we got our friend there in time. At this point, all we can do is wait for the toxin to wear off so he can start breathing on his own.
While we wait, let’s talk about other ways people have been poisoned by tetrodotoxin. In China, people like to eat cone snails. Many of these gastropod species are toxic. Like with horseshoe crabs, misidentification has led to poisoning.
Grey side-gilled sea slugs contained it and in New Zealand killed dogs who ate them on the beach. The blue ringed octopus is a beautiful, but venomous creature. It reportedly contains enough to tetrodotoxin to killed twenty-six humans. There are three reports of death attributed to the blue ringed octopus, two in Australia and one in Singapore.
Typically, pufferfish and other exposures have occurred in Asia. Interestingly, there’s archeological evidence of pufferfish consumption in Japan from 4000 years ago. Recently, tetrodotoxin been found in sea life in the Mediterranean and other countries. An intriguing theory called Lessepsian migration might explain this change. The Suez canal opened in 1869, allowing migration of marine life from Asia to the Mediterranean. Another theory suggests tetrodotoxin containing organisms are transferred from Asia to other places via ships when they drop ballast water. Natural disasters contribute. For example, the 2004 Indian Ocean tsunami caused marine migration.
Tetrodotoxin isn’t the only poison found in pufferfish. They can contain other toxins like saxitoxin and palytoxin. More on this in future episodes.
Surprisingly this potent toxin has potential therapeutic uses. Tetrodotoxin containing globefish were used in Japanese folk medicine to treat pain from leprosy. In the 1900s a Japanese physician used globefish ovary extract to treat muscle spasms related to another potent toxin, tetanus. Research is currently ongoing in several areas. Tetrodotoxin has been used to treat cancer pain and seems to be one of its most promising uses at the present time. It may improve brain damage in patients suffering strokes or cardiac arrest. It appears has some utility in the treatment of heroin and cocaine addiction.
Tetrodotoxin is also the stuff of witchcraft and legend. In Haiti it’s believed voodoo practitioners can turn people into zombies using a magical powder. Wade Davis, a famous ethnobotanist believed the power contained tetrodotoxin, though this theory has since been debunked. His book The Serpent and the Rainbow was turned into a horror film of the same name by Wes Craven.
Tetrodotoxin is so potent it has been used in murder. A case reported from China describes the following events. A man opened the door of his house to two assailants who injected liquid into his buttocks via syringe then fled. The victim tried to chase them but immediately became sick and unable to do so. He called 911, related this story then began gasping and stopped speaking. When doctors arrived ten minutes after the call, he was dead. Autopsy findings confirmed a broken needle in the patient’s buttock. Tetrodotoxin was discovered after the killers were caught and confessed.
I love doing this podcast because no matter how much I know about a topic I always learn new fascinating facts during my research. Did you know horseshoe crab smuggling existed? And is such a huge business horseshoe crabs are now threatened with extinction? I certainly didn’t. Horseshoe crabs are called living fossils because they’ve been alive for 440 million years. Long before dinosaurs existed. Now humans might bring an end to their prehistoric lifespan.
Why? Because horseshoe crabs are used in laboratory medicine to make sure things sterile. They have striking blue-colored blood. If you’re listening to the podcast, check out the YouTube video or go to the transcript on pickpoison.com to see a picture. It contains a compound called LAL and is used in labs around to the world to detect bacterial endotoxin. If you’ve gotten a flu shot, had a hip replacement or a stent, you’ve benefited from horseshoe crab blood.
Many countries have rules about how much blood can be drained, like humans some blood can be taken safely. However, smugglers often drain all the blood, killing the creatures off at a precipitous rate.
Getting back to Chris he starts breathing again and is weaned off the ventilator two days later. The dinner host also recovers. Fortunately for all involved, the only thing lost was Chris’ memory of the events and everyone’s rest and relaxation.
That brings us to the last question in today’s interactive podcast. Question number 4. Which famous explorer probably encountered, and survived, tetrodotoxin?
A. James Cook
B. Christopher Columbus
C. Francis Drake
D. Ferdinand Magellan
Post your answers on our Twitter feed @pickpoison1. I’ll post the answer in the next 24 hours.
This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings that have occurred periodically. Never try anything on this podcast at home or anywhere else.
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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.