Sweet

Want to know what toxin affects humans, but not bees? What contaminated substance is so valuable, people risk their lives to collect it? What popular natural substance was used in biological warfare in wars between Russia and Ukraine in the past? 

Transcript

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 patient survive this podcast? It’s up to you and the choices you make. Our episode today is called sweet and sugary. Want to know what toxin affects humans, but not bees? What contaminated substance is so valuable, people risk their lives to collect it? What popular natural substance was used in biological warfare in wars between Russia and Ukraine in the past? 

Today's episode starts at a music festival. Your friends have rented a house nearby and you took them up on their offer to stay for a night. After a day of great music, you crawl into bed in the early morning hours. Shortly thereafter, a banging sounds on your door. You pull the pillow over your head and try to ignore it. It increases in intensity. It’s your friend, yelling wake up. Her partner is sick. As you pull on a sweatshirt over your pajamas, you ask her through the door what's the matter? She says he feels dizzy and lightheaded. Your tempted to shout back, tell him to drink some water and go to bed, after all, it was a music festival with unhealthy food, copious amounts of alcohol in which he indulged to excess and all sorts of other mind-altering substances. Instead, you open the door to see what's happening.

Her partner is laying on the bed with his eyes closed. He looks sweaty. He responds to the sound of your voice, but says he’s keeping his eyes closed because he’s so dizzy. Two hours ago, just before you all left the festival, he developed nausea, vomiting, and diarrhea. He feels numb and tingly all over. A few minutes ago, he stood up to go to the bathroom and almost passed out, prompting your friend to wake you up.

He denies significant abdominal pain or fever. Your friend is not sick, nor are you or anyone else in the house. You ask him how much he drank this evening, he says too much to remember. Asking about substances, he says marijuana edibles, but denies other drugs. He also denies medical problems, medicines, or over-the-counter medicines and supplements.

He doesn't look great, but he's otherwise healthy and none of these symptoms are particularly concerning. You have some anti-nausea medicine in your suitcase. He agrees to a dose of ondansetron, or zofran. You tell him to give it 20 or 30 minutes to work and then take small sips of water. You say you’ll check on him again in the morning, now just a few hours away, but to wake you up in the meantime if he feels work. You go back to your room, sink into your bed, doubting you’ll hear much else.

Just as you're about to fall asleep, you hear a thud from the bathroom. You jump up and find the partner collapsed on the bathroom floor, covered in vomit. He ran in thanks to extreme urgency from diarrhea. He became dizzy and passed out. Before he could get himself up, he vomited everywhere. Fortunately, he fell on a fluffy bath mat and denies headache or other traumatic injury from passing out, but reports ongoing dizziness, vomiting, and diarrhea.

Well, conservative management at home does not seem to be working so you recommend he go to the emergency department for some IV fluids and IV nausea medicine. 

This is a fictional case, so of course, you’re the doctor.

In the emergency department, his chart notes he’s 41 years old. His temperature is normal at 98.6F or 37 Celsius. Interestingly, his heart rate is low at 42 beats per minutes, so is his blood pressure 100/60. His respiratory rate is normal at 18 with the pulse ox of 100% on room air.

He denies cough or flu symptoms. He's not having any urinary complaints and he doesn't have any significant abdominal pain, just some cramping with the vomiting and diarrhea. 

His appearance is the same, pale and sweaty. Other than the low heart rate and borderline blood pressure, his exam is unremarkable. Normal neurological exam, and muscle tone, normal lungs and no abdominal tenderness. You order several liters of IV fluids, IV nausea medicine and some basic labs. 

What do we make of these vital signs? It's difficult to know at this exact moment. One of the most common causes of passing out, syncope in medical terms, is called vasovagal syncope you've probably heard of it, you may have it. It’s when someone passes out due to a sudden drop in blood pressure. For example, it's common in young women with low blood pressure at baseline, and if they stand up quickly or stand for a prolonged period of time, then the blood pulls in their feet and doesn't get to their brain. To fix this problem, the body puts the brain on level with the feet, by passing out very briefly and restoring circulation. The vasovagal part of the name refers to the vagus nerve. The heart, like other organs, has both sympathetic, fight or flight, and parasympathetic enervation, rest and digest. The vagus nerve is parasympathetic, responsible for slowing your heart rate. If you have too much vagal tone from this nerve, your heart rate stays low for example when you stand up, rather than increasing to increase cardiac output and blood flow to your brain. 

What causes increased vagal tone? Tons of stuff. Most of which are perfectly normal physiological responses. Think rest and digest, eating, deep breathing all increase vagal tone. Yoga, mediation, extreme temperatures, a cold shower or a sauna. Athletes naturally have increased tone, why runners have low heart rates. These are all normal physiological responses, vasovagal syncope occurs when the body essentially over corrects. Why am I talking about this? Because vomiting is a big thing causing increased vagal tone. Which is why when you throw up sometimes you feel like you're gonna pass out and you might get extremely sweaty.

He says, “I'm gonna throw up.”

You grab a basin and the nurse goes to get the nausea medicine. In an elderly patient, I’d be more worried about the low heart rate. He’s otherwise healthy, so the most likely cause here, is a vagal response to vomiting. Some of you might be worried this low heart rate is causing the low blood pressure, and certainly that's possible. But it's just as likely, his low blood pressure is from dehydration thanks to the copious amount of alcohol he ingested at the festival along with the vomiting and diarrhea. 

I'd take notice of these vital signs, but at this point, I wouldn't get too excited about them. I’d expect them to improve with anti-nausea medicine and IV fluids. It is worth checking an EKG to make sure we don't see anything unexpected. 

A few minutes later, the tech hands one to you, showing sinus bradycardia, which means a slow but normal heart rate, without evidence of heart block or conduction problems. You tell the nurse to let you know if anything changes and move on to the many other patients waiting to be seen.

An hour later, the nurse updates you saying nothing has changed. Ok, good he hasn’t gotten worse, but a little odd he hasn't improved. His heart rate is still in the 40s and his blood pressures about the same. He continues to have vomiting and diarrhea, now to the point of fecal incontinence. You're in the middle of about 100 more emergent issues so you order more nausea medicine and more IV fluids, thinking maybe he just needs more time.

You go back in the room to check on him, now about two hours after arrival. He’s wobbling in the middle of the room, you and your friend grab him just in time to keep him from falling. Against the nurse’s advice, he got out of bed to use the bathroom and became very dizzy.

All right, it seems like there's more going on here than a simple case of nausea and vomiting from too much alcohol, food poisoning, or gastroenteritis ie a stomach virus. Certainly cases of gastroenteritis and food poisoning aren't cured in the emergency department, but most patients feel much better after a few hours and are well enough to go home with some nausea medicine for oral rehydration. 

The differential diagnosis for nausea and vomiting is basically unlimited as we've discussed before. The unusual symptom here is the low heart rate. Most people with vomiting and diarrhea have high heart rates due to dehydration, and most of those are fixed with a bag or two of IV fluid. Why is his heart rate persistently so low? It’s not uncommon to see transiently low heart rates from increased vagal tone, generally its minutes, rarely it lasts longer, but this seems like too long. 

So let's talk for a few minutes about bradycardia. As I alluded to earlier, there are several different kinds of slow heart rates. You can have conduction problems where nerve impulses aren't conducted through the heart, this can result in different types of heart block. Sometimes these patients may need a pacemaker. Does our patient need a pacemaker? That's question number 1. 

A.                Yes

B.                 No

Answer: B. No, he doesn’t need a pacemaker. Yes, he does have a low heart rate, but in his case, the EKG showed a normal, just slow heartbeat. That’s not normally an indication for a pacemaker. Usually those are for conduction problems causing the low heart rate. 

Is this bradycardia dangerous. Yes and no. He does have signs of hypoperfusion, meaning his circulation isn't great, it probably is the cause of his low blood pressure, now that we’ve treated and eliminated dehydration with several bags of fluid. More importantly, the dizziness and passing out with standing, means his heart is beating too slowly to support his circulation. That said, his circulation is fine when he's laying down, he's awake with good pulses an adequate, if low blood pressure.

Is there something else we can do to treat this? Atropine did I hear you say?

Atropine if you remember is a cholinergic drug, meaning it works opposite the vagus nerve, and increases the heart rate. You and your friend maneuver her partner back into bed without him falling. You ask the nurse to bring a bedside commode so he won’t try to walk to the bathroom and order more nausea medicine. 

You ask him again about the music festival and his exposure to substances. He repeats again he had a lot of drinks, a lot of marijuana, but doesn't use substances and didn't do so at the festival at least as far as he remembers. He does admit that some parts are fuzzy.

Could this be a drug of abuse? Plenty of those at music festivals. We talked on a prior episode, Adulteration, about a fentanyl adulterant that causes a low heart rate. Could this be metatomidine? It’s a great thought, but he denies opioid use, you were around him much of the time yesterday and at no point did he show any signs of fentanyl use. Kind of unlikely. Sympathomimetics like cocaine and meth can have significant cardiac effects, generally ischemia, like a heart attack, and cause a rapid heart rate. Also doesn’t fit. There really aren't many drugs of abuse causing significantly, sustained low heart rates.

What does cause a low heart rate? Hypothyroidism, or low thyroid, heart attack, Lyme disease are on the list. None of these really fit. We've talked many times about calcium channel and beta blockers, blood pressure drugs that also lower your heart rate. Could he have taken something like that? Possible, it fits with his vital signs, but how would he be exposed? Was it a contaminant in his marijuana? Again, not the most likely scenario. Clonidine we discussed before, and it's analog tetrahydrozoline found in Visine. Did someone spike his drink with Visine? Well, anything is possible, especially toxicology. But if you have significant bradycardia, I'd expect more of an altered mental status, at least some lethargy which he doesn’t have.

Electrolyte disturbances like low potassium can cause it, though in that case I'd expect to see more changes on his EKG, but his labs are pending, so we'll find out. Exposure to organic phosphates, like in pesticides, sarin or VX gas could cause it. Certainly, they would cause vomiting in diarrhea. But I'd also expect muscle weakness, and quite frankly more serious, life-threatening symptoms. If you remember, bradycardia is one of the killer Bs. He’s certainly not well but, he's not exactly critically ill or dying at this moment either.

What about the… Stuff?” your friend says, gesturing vaguely in the direction of his groin. 

“The stuff?” You ask. 

The ummm…stuff… for, you know.” 

The patient doesn't answer. You have no idea what she's talking about. Her cheeks are turning red.

“The whiskey shots, with the honey,” she says.

This sounds like a cocktail, not a medical problem. Question 2. 

What toxin is often associated with honey?

A.                Tetrodotoxin 

B.                 Botulism

C.                 Arsenic

D.                Cyanide

Answer: B Botulism toxin is often associated with honey. Is this botulism toxicity? No, definitely not. He would have flaccid paralysis, which is not an issue here. 

In fact, honey, has been contaminated with a number of things. It's a natural product, obviously, and while pollenating, bees can incorporate toxins from other nearby plants. Datura, ie jimsonweed, causing anticholinergic toxicity and altered mental status. Belladonna, even morphine if poppy flowers are nearby.

Generally, these are rare occurrences, not causing significant toxicity in humans even after exposure. But there is a toxin, whose presence in honey is actually cultivated, sought after and expensive.

Mad honey? You ask

“No way it's that,” he says. “My friends mixed it in with whiskey and we all drank a bunch of shots. They told me it's an aphrodisiac.

He doesn't think this is mad honey poisoning. Do you? Time to pick your poison? Question 3. 

A.                True

B.                 False

Answer: A true. These symptoms definitely fit with mad honey poisoning. First what exactly is mad honey? It's honey contaminated with Rhododendron plants. Rhododendrons are poisonous, they contain grayanotoxin, and if Rhododendrons grow nearby to the beehives, the bees may produce mad honey rather than regular honey. 

What happens if you’re exposed? The symptoms start within 30 minutes and typically last around six hours. Grayanotoxin is a sodium channel poison. It binds to sodium channels, which we have in all of our cells, holding the channels open. This means the cell can't conduct impulses normally. This accounts for the numbness and tingling that a lot of people report. In the GI tract it causes nausea, vomiting and diarrhea. The diarrhea can be so severe it causes incontinence. 

In the heart, grayanotoxin basically overstimulates the vagus nerve, leading to too much vagal tone, leading to bradycardia. Sometimes it can cause more severe conduction disturbances, including complete heart block. Despite this, patients rarely require pacemakers, because the symptoms usually resolve after a few hours. In fact, in a paper looking at nearly 1,200 patients who were exposed to mad honey, no deaths were reported. 

Do people ingest mad honey by accident? This is toxicology so you know anything is possible, but no most of the time it's not ingested by accident but by intention.  Mad honey is I don’t know if cultivated is the right word exactly, but beekeepers intentionally produce it in many areas like Turkey. It looks different than regular honey, it has a dark red color. It also has a bitter taste. It’s worth so much people literally risk their lives to collect it. The two big regions it comes from are Turkey as I mentioned and Nepal. In the Himalayas. If you want to see some crazy videos, look this up. They aren’t battling bees, but the environment. Men on homemade rope ladders dangling from the sides of not just a mountain but the Himalayas, collecting mad honey from huge hives on the cliffs.  In the West, it can cost as much as $150 per pound. In Asia people reportedly pay thousands of dollars per kilo for rare forms of mad honey. 

So why eat it? Why pay so much for it? Great question. 

Mad honey and its properties have been known since ancient times, in fact it's believed to be an early biological warfare agent, more on this in a few minutes. Historically it was used to treat gastrointestinal problems, like indigestion and gastritis, arthritis, flu and diabetes. It’s still used by some people for these reasons today. The biggest reason it costs so much? It’s use as an aphrodisiac, especially popular in Asia. It’s therefore not surprising 75% of mad honey complications are reported in men, often middle-aged.  

Mad honey is also reported to be a hallucinogen, particularly in ancient times. So much so, some wondered if it’s the source of visions at Delphi, the Greek oracle. Hallucinations are not part of the reports in modern medical literature. It’s unclear if this is an issue of accuracy in historical sources or if the composition of mad honey has changed over time. Grayanotoxin concentration itself is cyclical. Mad honey is often more potent if collected in the spring. As I said, it’s a natural product, reflecting plants nearby the hive, so the composition can easily change.  

What about the bees?  Question 4. What effect does grayanotoxin have on the bees? 

A.    Affects flight

B.     Affects reproduction

C.     No effect

Answer: C Interestingly enough, grayanotoxin has absolutely no effect on the bees. 

Back to our patient. What is the treatment after exposure to mad honey. Did we do the right thing? Is there an antidote? The treatment is generally supportive care. The symptoms generally last an average of six hours, a day at most. Atropine can be helpful for the slow heart rate. Grayanotoxin doesn’t directly cause anticholinergic toxicity, but it does result in excessive anticholinergic symptoms, specifically in the gastrointestinal tract and vagus nerve. Permanent pacemakers aren’t required as I mentioned, given the short duration of the symptoms, but some patients do require temporary pacemakers. What’s the difference? A pacemaker is a device implanted during surgery. A temporary one is a wire floated into the patient’s heart via a large catheter, attached to a machine outside the body. Once the patient recovers, you pull the wire out and that’s it. 

The nurse tells you his heart rate is now in the 60s after atropine, and his blood pressure is improving to 110/65. 

Ok, so lets talk about the really fascinating part of this, how it’s been used in warfare as a biological weapon. Exposure is documented as far back as 401 BCE, historian. Xenophon, described its effects on Greek soldiers in Turkey after coming upon hundreds or thousands of beehives, eating the honey and becoming disoriented, with vomiting and diarrhea. It knocked the soldiers out for about a day or so, until they recovered. Mithradates in 65 BCE, used it intentionally to poison the Romans. He staged a strategic withdrawal, placing combs of mad honey in the path of the oncoming army. The soldiers reportedly ate the honey and became confused and were easily killed, reportedly 500 to 2000 victims. 

Warfare between Ukrainians and Russians, I’m sure you know didn't start in modern times. In 946 Queen Olga of Kyiv sent several tons of fermented honey to the Russians, then massacred 5000 confused soldiers afterwards. I don’t know if the Russians remembered this, in 1489, when they put mad honey in mead, then “abandoned it”. This time reportedly 10,000 Tartars were slaughtered by Russians. 

Back to our patient. His heart rate improves and the vomiting and diarrhea gradually subside. He’s discharged from the Emergency Department without sequalae after 6 hours. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.

Last question in today’s podcast and our pop culture consult. What movie adaptation of an Agatha Christie book featured mad honey? 

A.    A Haunting in Venice

B.     Death on the Nile

C.     Murder on the Orient Express

Follow the Twitter and Instagram feeds both @pickpoison1 for the answer. Remember, never try anything on this podcast at home or anywhere else. 

Thanks for listening. It helps if you subscribe, leave reviews and/or tell your friends. Transcripts are available at pickpoison.com. 

 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. Until next time, take care and stay safe.