Toxic Tea Episode 3
Interested in toxic tea? The poison associated with werewolves? And so potent it was used on poison arrows to hunt bears, ibexes and even whales. A substance used as both a poison and a medicine? Listen to hear more!
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.
Interested in toxic tea? The poison associated with werewolves? One so potent it was used on poison arrows to hunt bears, ibexes and even whales. Then stay tuned!
Our patient today is a forty-five-year-old man who presents to the emergency department complaining of numbness and tingling. He reports the symptoms initially started in his mouth but have now spread to his entire body. He feels lightheaded and dizzy, like he might pass out. He also has palpitations, a racing heart rate, and shortness of breath.
He’s laying on the stretcher with his eyes closed, lethargic. His skin is pale and clammy. You glance up at the monitor for his vital signs. His heart rate is 140 bpm, well above upper limit of a normal of 100 bpm. His blood pressure is 60/40, very low. He is breathing rapidly at twenty-four breaths per minute, almost twice the normal rate. His oxygen level is normal.
He opens his eyes, barely, to answer questions. He says his symptoms started one hour prior to arrival, first with the just the numbness and tingling, then progressively worsening. He denies ingestion of illicit drugs, an overdose, or a suicide attempt. He reports that he takes medicine for high cholesterol as well as occasionally acetaminophen and ibuprofen (brand names Tylenol and Motrin in the US) for arthritis pain in his knees.
The nurse puts in an IV and starts IV fluids to help raise his blood pressure. His heart rate shoots up to 180 bpm as an alarming rhythm races across the monitor. He clutches his chest and his blood pressure drops even lower. It’s a lethal arrhythmia -- ventricular tachycardia. You have a million more questions you want to ask the patient, but this is no time for questions. You have to do something to treat him first.
You order amiodarone an antidysrhythmic medicine and hope it stops the ventricular tachycardia. On a positive note the patient still has a pulse. Nevertheless, the nurse puts defibrillator pads on his chest, because if he loses his pulse we will need to administer electrical shocks.
Ventricular tachycardia means the heart is beating rapidly. Too rapidly. It isn’t pausing and relaxing for the heart chambers to fill with blood. This means that the patient’s circulation is impaired, not enough blood is being pumped to the rest of his body. At this moment he still has a pulse, so the circulation is enough to keep him alive. But the low blood pressure and clammy skin indicate shock. If the v. tach doesn’t stop, he might not be alive for long.
While waiting, let’s be honest crossing your fingers, hoping the amiodarone works, you review the patient’s medications. Acetaminophen and ibuprofen are definitely not responsible for these symptoms, even in overdose. Neither is any anti-lipid agent for cholesterol. As for medical problems, heart disease is one of the most common causes of ventricular tachycardia.
After a few minutes, some color returns to the patient’s face. His heart rate slows, his blood pressure improves and he’s able to answer more questions. He doesn’t have any prior history of heart disease and wasn’t having any chest pain, leg swelling or other symptoms of cardiovascular disease prior to today. This certainly doesn’t exclude heart disease as the etiology of his ventricular tachycardia, but it does make it less likely. This isn’t a cardiology podcast it’s a toxicology podcast.
So what are the poisons that can cause ventricular tachycardia?
This isn’t question number one in today’s podcast because the list is way too large. Toxins that cause V. tach include everything from over-the-counter drugs like diphenhydramine i.e. Benadryl, to antidysrhythmics themselves, to plants, jellyfish, antidepressants, antipsychotics, and drugs of abuse.
You ask again about over-the-counter medicines, he denies anything other than what he previously mentioned. As I’ve said in previous episodes, toxicologists love to ask about supplements. At first, he denies them, but then says he took some herbs sent to him by his sister. His sister obtained the blend from a Chinese herbalist. He doesn’t know what they were, but they were supposed to help his arthritis pain. When you ask for more details about the ingredients, he says it was a bunch of brown leaves that tasted terrible.
The monitor starts beeping loudly, his heart rate increases and his blood pressure again drops. You notice the heart rhythm is changed. It’s still ventricular tachycardia, but it looks different. The rhythm seems to be alternating between two different types, or morphologies, of beats. You ask the tech to run an EKG. After a minute, she rips the paper off the machine and hands it to you.
Before you can read the EKG, the patient’s eyes roll back in his head. He passes out. You immediately put your fingers on his neck, there’s no pulse. If you listened to Episode 1 Love Hurts, you know the first thing to do in a code. Check your own pulse, i.e. remain calm.
One nurse starts CPR. You tell the other nurse to ready the defibrillator. When it’s charged, you say clear and shock the patient, hoping the charge will reset his heart back into a normal rhythm. You also give another dose of amiodarone. After several shocks, to your relief, you get a pulse back. You turn your attention to the EKG in your hand.
It shows by bidirectional ventricular tachycardia. An extremely rare arrhythmia. V. tach is a dangerous, but not particularly uncommon rhythm. Bidirectional ventricular tachycardia, a specific type of v. tach, on the other hand, is extremely rare. It is again, caused but heart disease and other medical problems. But it can also be caused by toxins specifically only two toxins, at least as far as I’m aware.
Question number one which of the following compounds can cause bidirectional ventricular tachycardia?
A. Ginseng
B. Aconitine
C. Digoxin
D. Arsenic
Answer: B and C. Aconitine and digoxin.
Now your pulse is racing out of control. Why? Because this is proof that the patient ingested a very lethal poison. This EKG finding pretty much tells us what happened. No further testing required.
This isn’t digoxin toxicity. If it were the patient would’ve had a slow heart rate. The onset of symptoms wouldn’t have been this quick. And he wouldn’t be complaining of numbness and tingling. See Episode 1 if you’re interested in more details.
This is a classic case of aconitine poisoning. The patient took the herbs for his knee pain. Digoxin isn’t used as an anti-inflammatory. Aconitine is in traditional Chinese medicine. We’ve arrived at the answer while still at the bedside, very shortly after the patient arrived. That’s not always the case in toxicology, with lab tests that can take weeks to result. While it’s great for us that we’ve discovered the cause, this is not great news for our patient.
What now?
Unfortunately, there is no antidote for aconitine poisoning. The treatment is supportive care and we’ve done just about everything we can do already. You start a continuous amiodarone infusion to help. Keeping an eye on his heart rhythm, treating with antidysrhythmics, and doing CPR and advanced life support if necessary. Aconitine is a lethal poison, the only upside is that it has a short half-life. Meaning that it doesn’t last for long, before it’s broken down by the body. Short in this case meaning three or four hours.
There is one other option. It’s drastic and not indicated at this moment, since we’ve gotten a pulse back and his vital signs are stable. For now. It’s a good idea to call the cardiothoracic surgery team and alert them to the potential need for ECMO. What’s ECMO, Extracorporeal membrane oxygenation? Essentially its a cardiopulmonary bypass machine that circulates and oxygenates the blood. ECMO is extremely invasive and can cause a lot of serious complications including bleeding, blood clotting, loss of limbs, seizures and strokes. If the patient’s life hangs in the balance, then these risks are worth it and we will pull out all the stops. But right now his heart is holding its own and he’s probably better off not on ECMO.
What is aconitine and why would anyone include a lethal toxin in a mix of Chinese herbals to help with knee pain? First, let’s talk about aconitine, then come back to its absolutely fascinating history a bit later in the show.
Aconitine, also called aconite and aconitum, has been used since ancient times for both poisonous and medicinal reasons. It’s found in plants of the genus Aconitum. Plants like monkshood and wolfsbane. Monkshood is so-called after the shape of the flower. If you’re listening to the podcast check out the YouTube video or go to pickpoison.com to see a photo. Wolfsbane gets its name because the planet was used to poison animals such as wolves and panthers. Aconitine been called also the Queen of Poisons. One teaspoon of pure aconitine is enough to kill several people.
It has been used in traditional Chinese medicine for thousands of years. It was first recorded two thousand years ago in Shennong’s Materia Medica, the very first Chinese herbal medicine text. It was also used in ancient Indian ayurvedic medicine. The ancient sources all acknowledge the dangerous nature of aconitine and prescribed strict dosing parameters. So how has a substance been used medicinally for thousands of years when one dose almost killed our patient?
Was the patient’s sister trying to kill him? Maybe. Aconitine has certainly been used with malicious intent for as long as it’s been used for therapeutic reasons. Ovid, the Roman poet, wrote “fearsome stepmothers mix learned aconites.”
In traditional Chinese medicine aconitine has a number of different uses. It also has a number of different names including chanwu and fuzi. It’s used as an anti-inflammatory to treat rheumatism and joint pains, as a cardiotonic to treat edema or swelling, as also used for abdominal problems, menstrual pain, and asthma.
Question number two according to traditional medicine texts what reduces the toxicity of aconitine?
A. Grinding
B. harvesting only the leaves
C. boiling
Answer C. boiling
You ask the patient how he prepared the herbs his sister sent. He boiled the water, mixed in a few teaspoons of leaves, then drank the decoction. There were no instructions included with the mixture. His sister had told him to make a tea and drink it if his knee pain was particularly bothersome.
This isn’t the preparation recommended in traditional Chinese teaching. We’ll never know if the patient would’ve avoided toxicity if he had prepared the aconitine properly. Traditional Chinese medicine not only gives strict instructions about the dose, but strict instructions for aconitine preparation. Traditional Chinese and Indian texts recommend boiling the herb for extended periods of time, in some cases for up to two days. Thereafter, minimal toxicity is reported. While this is an unregulated and unscientific approach to such a dangerous poison, we do know that parboiling reduces toxicity of some plants. Cassava and poke weed are two examples of potentially toxic foods that can be made safe if properly prepared with parboiling. At a bare minimum, the aconitine leaves should be boiled for at least an hour.
He doesn’t think his sister was trying to kill him, so it’s more likely the instructions were lost. Either lost in translation or lost in transmission. Regardless, our patient didn’t get the message on how to, at least potentially, reduce the toxicity.
How does aconitine work? What does it do in the body that makes it so toxic? Aconitine plants contain different alkaloids of varying potency and toxicity. The alkaloids work as sodium channel openers. In the nervous system this effect is somewhat like the effect of local aesthetics such as lidocaine and the reason why patients develop numbness and tingling.
In the heart, this has a far more dangerous effect. It opens sodium channels in cardiac muscle and keep keeps them open. This causes uninhibited excitation of the heart muscles, in turn leading to ventricular tachycardia. The classic finding of bidirectional ventricular tachycardia is basically the arrhythmia spiraling around the heart’s electrical system in a circular pattern. Aconitine such a potent and reliable toxin, that it’s used in the lab for experiments with sodium channels.
Interesting pharmacological properties of the plants have been exploited by practitioners of traditional medicine. Aconitine containing plants have a mix of different compounds, as I’ve mentioned. Not surprisingly, those that are less toxic are typically more desirable from a medicinal standpoint. The strict instructions given for preparing, like boiling the plant or baking the leaves, have been shown, using modern scientific techniques, to reduce the amount of more dangerous aconitine alkaloids.
Second, the traditional method of mixing different herbals together may exploit complex pharmacological drug-drug interactions to reduce toxicity. Ginseng for example modulates enzymes that metabolize aconitine and in lab models reduces its toxicity. Licorice administered together with aconitine has also been shown to reduce toxicity in rat and mouse models. Fascinating that doctors figured this out thousands of years ago before anyone knew about enzymes or drug metabolism.
Despite safer methods of preparation then our patient used, I personally wouldn’t take aconitine under any circumstances. Its therapeutic window is too narrow, as we say in toxicology. Meaning the dose for a therapeutic effect and the dose that causes toxicity are too close together for either comfort or safety.
Narrow, like a razor’s edge, a fact acknowledged by ancient texts. To quote a translation of a text from the second century BCE the Huainanzi. Apologies for butchering the pronunciation, “For all things under the heaven, nothing is more vicious than the poison of aconite. Yet a good doctor packs and stores it, because it is useful.”
In modern medicine we thankfully have other, safer drugs to treat the problems for which aconitine has been used. The risk of toxicity is much higher than any benefit it might possess.
For as long as it’s been used in medicine, it’s also held a place in mythology and magical lore. Cerberus the three-headed dog guarding the Greek underworld was said to slaver aconitine. This is interesting because some of the features of aconitine poisoning resemble rabies, making it a cool connection made by the Romans. Ovid wrote of Athena sprinkling it on Arachne when turning her into a spider. It has been suggested that the Emperor Claudius was killed by his wife Agrippina using aconitine.
Question # 3: What magical properties have been attributed to aconitine?
A. The ability to fly
B. Turning people into werewolves
C. Invisibility
D. All of the above
Answer D. All of the above
Aconitine was said to be part of the flying ointment that witches applied to brooms to allow them to fly. It was thought to have the ability to turn people into werewolves. It was even said to give witches is invisibility when carried in lizard skin.
In the modern story of Harry Potter, Severus Snape brews a wolfsbane potion for Professor Lupin to prevent him from turning into a werewolf. Lycanothropism, is the delusion that one is a werewolf. This was reportedly treated with wolfsbane in the Middle Ages. Doubtful it improved patient outcomes however.
Aconitine is so toxic it has also been used in warfare. The Greeks used it to poison spear tips. Poison arrow tips were also used in hunting bears, Ibexes and even whales in Alaska.
Recently, aconitine was touted as a treatment for COVID by the president of Kyrgyzstan causing several people to be admitted to the hospital with aconitine poisoning. COVID is bad enough without being poisoned on top of it.
What happened to our patient? If you made the right choices, he survived. The antidysrhythmics worked and after several hours his symptoms gradually resolved. 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. Several years ago in San Francisco, two people were poisoned and one died after ingesting aconitine for medicinal purposes.
This brings us to the last question #4, in today’s interactive podcast.
Which character from Greek mythology attempted to poison someone with aconitine?
A. Medusa
B. Penelope
C. Persephone
D. Medea
Post your answers on our Twitter feed @pickpoison1. I’ll post the answer in the next 24 hours.
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