Murder and Medicine
Want to know what poison is still used as medicine? Why it’s called the King of Poisons and what it has to do with the very first antibiotic? 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 patient survive this podcast? It’s up to you and the choices you make. Today’s topic has been highly requested, so I’m excited to talk about it. This episode is called Murder and Medicine. Want to know what poison is still used as medicine? Why it’s called the King of Poisons and what it has to do with the very first antibiotic? Listen to find out!
Today’s episode starts in the emergency department. Your next patient is a sixty-year-old man with a chief complaint of diarrhea. He’s pale and ill appearing. His wife is pressing a cool compress to his forehead. The patient reports light-colored watery, liquid stools. He’s vomiting and has severe, crampy abdominal pain. He denies blood in the stools and hasn’t had fever. You ask if anyone else in the family is sick, thinking of food poisoning. He says no. He hasn’t been camping or drinking out of mountain streams, making a parasite infection less likely. Also, he denies recent travel or antibiotics.
On past medical history, he notes high cholesterol for which he takes atorvastatin, brand name Lipitor. He denies other medicines, over-the-counter drugs or supplements, as well as any tobacco, alcohol and drug use.
His vital signs are: temperature 98.5 Fahrenheit or 36.9 Celsius, heart rate 105 beats per minute, respiratory rate of eighteen and oxygen saturation 100% on room air.
Diarrhea isn’t the most exciting chief complaint, though it is a very common one. In the US, it’s rarely an emergency. You order labs to check his hydration status and his electrolytes. His elevated heart rate suggests mild dehydration and he’s vomiting, so you also order IV fluids. In patients with diarrhea and abdominal pain, a CT of the abdomen can be useful to check for diverticulitis, an infection in the colon. You order that as well.
We rarely order stool studies for bacterial or parasitic infections in the ER as they are low yield outside of specific scenarios. In addition, they take days to come back, so we won’t get the results. C. diff tests we might order. Infections use to be solely hospital acquired, but can now occur in the community. If he gives a stool specimen while in the ED, it won’t hurt to check.
As I mentioned in the last episode, when we hear hoofbeats we’re supposed to be thinking of horses not zebras, common things being common. Diarrhea in the ER is most commonly viral, like stomach viruses, or mild cases of food poisoning.
The labs come back, without signs of infection, but showing significant dehydration. His creatinine, a measure of kidney function, is elevated at 3.2 mg/dL or 283 mmol/L. Patients always think they’re dehydrated after a few days of diarrhea, but in healthy patients, it takes a lot longer than that. So surprising this occurred with only 2 days of symptoms, but not impossible. His CT scan is negative. On your way into the room to discuss his results, the nurse is collecting the stool specimen. It’s liquid, watery with a whitish color.
Most often the ER treatment of diarrhea is IV hydration, then discharge with expectant management and continued oral rehydration. In this case, however, you tell him he requires admission, given the acute kidney injury, for ongoing IV hydration. Side note, it’s extremely fortunate we found a reason to keep him in the hospital, back to this in a few minutes.
Your hospitalist colleagues take over his care, anticipating another day or so of IV fluids. The patient’s c.diff test is negative, so are the other stool studies they order for bacterial and parasitic infection. The patient isn’t improving. He continues to complain of abdominal pain, vomiting and diarrhea. Also, the creatine doesn’t go back down to normal.
The hospitalists start looking for zebras. The patient becomes more tachycardic and develops a low blood pressure, neither of which is responding to fluid. If this is dehydration, even from really severe diarrhea, both should improve with hydration. So should his kidney function. Not only is he not improving, he’s actually getting worse. They add antibiotics, just in case, though no infection’s been found.
The hospitalists consult you in your capacity as a toxicologist. They’ve already consulted gastroenterology and infectious disease without any luck. You start the consult and begin by reviewing the patient’s chart in further detail, noting three visits to the emergency department in the preceding two months, all for abdominal pain and diarrhea.
Scrolling through the chart, you think this might be the first consult you’ve ever gotten for persistent diarrhea. Certainly, significant diarrhea is expected with opioid withdrawal. Let’s say the patient had an opioid dependency he didn’t tell us about, it wouldn’t be the first time this happened. He’s now been in the hospital for three days. Opioid withdrawal would be improving on its own, even without any intervention. Tons of drugs have the side effect of diarrhea, as anyone who’s ever taken an antibiotic can tell you. Chemotherapeutics cause a lot of diarrhea, but he doesn’t have cancer. Laxatives obviously, he’s not getting those. Many plants cause gastrointestinal distress, aloe and mushrooms for example, but again symptoms don’t last long.
Plenty of toxins cause diarrhea but typically the diarrhea is a minor concern compared to other aspects of poisoning. Radiation causes diarrhea, but more concerning low blood counts, our patients remain normal. Lithium can cause diarrhea, and a lithium level is easy to send, but he’d have other signs of toxicity like a tremor. Colchicine is notorious for diarrhea, but if this were real colchicine toxicity he’d have had a cardiac arrest by now. Same with thallium, yes to diarrhea, but no excruciating neuropathic pain.
Nothing in his chart for this visit raises any red flags. But 4 visits to the ED in 2 months isn’t normal unless this is cannabis hyperemesis, every ER doctor’s least favorite diagnosis. He denied marijuana use and his urine drug screen was negative.
There is one toxin strongly associated with gastrointestinal distress and diarrhea. Particularly stools of this particular description. Question number 1. What is it?
A. Cyanide
B. Organophosphate toxicity
C. Arsenic
D. Botulism
Answer: C Arsenic. I do like organophosphate toxicity and cholinergic poisoning for diarrhea, but the patient doesn’t have any other symptoms like the Killer Bs, bronchorrhea, bradycardia and bronchospasm. Ie a slow heart rate with wheezing and fluid in the lungs. Botulism causes diarrhea, but also paralysis, and cyanide, acidosis and cardiac arrest.
Leaving us with arsenic, a classic cause of abdominal pain and diarrhea. You treated him in the Emergency Department. Why didn’t you catch this? Good question. This case, though fictional, is a real-life scenario. So let me explain.
Arsenic as a podcast topic has been highly requested, most recently by an emergency medicine colleague of mine. Years ago, he was in close proximity to a person murdered by arsenic. Telling me about the case, he noted the victim presented to the ER and was discharged a few days before his death. He asked me a question. When a patient has diarrhea and abdominal pain, complaints every ER doctor treats multiple times per day, and thousands of times a year, how in the world do you catch the case of arsenic toxicity most of us will never see? This is a question I routinely ask myself.
There are a few clues, but I think we have to be honest. The medical literature as well as the media confirms many patients are seen in the ED and discharged with presumed viral gastroenteritis, or a stomach virus. Even after admission to the hospital, the diagnosis is often made on postmortem exam. Do I think I could do better than your average ER doctor? While I’d like to answer yes, the honest truth, probably no. We certainly can’t, and shouldn’t, be sending arsenic levels on every person with diarrhea. It’s difficult to have a high level of suspicion, as the history in these cases is lacking for obvious reasons. We got lucky in this case our patient required admission due to dehydration and kidney failure. In real life, he probably would’ve have been sent home.
What are the clues? First, is the repeated ED visits. Many victims are poisoned repeatedly over time before the fatal dose. No one gets a stomach virus 4 times in 2 months. That said, patients with undiagnosed inflammatory bowel disease or rare zebras like porphyria also present repeatedly for the same symptoms.
Second, the stools themselves are a clue. The classic description is rice-water stools, liquid and whitish in color, like the water in which you’ve soaked rice. This is also a classic description for cholera infection, back to this in a few minutes. The last clue is on the EKG. This is Question #2, for the medical professionals. What EKG change supports the arsenic toxicity?
A. QTC prolongation
B. ST elevation
C. ST segment scooping or
D. J point elevation
Answer. A. QTC prolongation is a side effect of arsenic toxicity. Again, this is nonspecific as it can result from electrolyte disturbances and medicines used to treat diarrhea, like loperamide or Imodium.
In truth, I’d be relieved if I made diagnosis antemortem, while the patient was still alive, rather than postmortem. Arsenic toxicity is tough, one of the reasons it remains popular with poisoners, even with modern medicine at our fingertips. The fact arsenic resembles cholera plays no small role in it’s popularity with murderers. In the past, cholera was extremely common, as was death after infection. Arsenic poisoning in the past resembled death from natural causes, thus it’s title, the King of Poisons.
Arsenic toxicity has been well known for thousands of years. It’s been around since at least 2,000 BC as a byproduct of copper smelting. The word arsenic is derived from Persian and Syriac words incorporated in Greek as ‘arsenikon’ meaning potent.
It was used as capital punishment in Korea and China. During the Joseon Dynasty in Korea nobles were executed with sayak, a mix of poisons containing arsenic. It was believed it was better than hanging or decapitation, though it’s difficult to say if that was actually true. Apparently, the convicted person was put into a hut, forced to drink the liquid, then the hut was heated up, to speed up the poisoning, with some victims sustaining burns as a result.
Arsenic’s popularity in murder really starts with the Borgias in medieval times. The family used it to murder political rivals and gain wealth and status. Lucrecia Borgia is often portrayed as a murderess, though more recent evidence suggests it was her family, not her. Another case of poison being misattributed as a woman’s weapon. It’s said the Borgia’s used cantarella, a mixture of poisons, speculated to include arsenic, copper and phosphorous, though evidence of its composition and in fact its existence is lacking.
Your phone rings, interrupting your thoughts. The hospitalist tells you the patient is delirious and just had a seizure. You recommend a spot arsenic test and a twenty-four-hour urine arsenic collection. Because he is sick and getting worse, I’d treat empirically for arsenic toxicity. The spot urine will come back later today or tomorrow, the 24-hour test in a few days. By the time we get the results, it might be too late. He’s headed down the seizure, coma, death pathway.
You do wonder why he’s getting sicker while in the hospital. Certainly, arsenic toxicity can start a cascade of symptoms, but on prior visits to the ER he improved with supportive care. He needs immediate treatment, so let’s focus on that and ask questions later.
Question 3. What is the treatment for arsenic toxicity?
A. activated charcoal
B. Chelation
C. Whole bowel irrigation
D. Hemodialysis
Let me give you a hint. Arsenic is a heavy metal. The answer? B. chelation. If you chose the other answers, I regret to inform you, your patient died. Charcoal does not bind to heavy metals. Whole bowel irrigation removes toxins still inside the gut, probably not the case here. Hemodialysis removes very little arsenic.
Chelation is a critical intervention for our patient. In cases with high clinical suspicion, like here, treatment should be started prior to confirmatory test results. There are several options. In the US, we have 2 choices for chelation, dimercaprol, an intramuscular preparation, or succimer given orally. Dimercaprol is indicated for sick patients, succimer for mildly ill patients with subacute or chronic toxicity. In Europe, there’s a third option, DMPS which can be given by any route.
Chelators work by binding to heavy metals, inactivating them so they can be excreted. It sounds great, and it does work, but the data for chelation for any heavy metal poisoning is never as clean as we toxicologist would like. There is some animal data suggesting chelation while lowering blood arsenic levels, might increase the levels in the brain, obviously not ideal.
Dimercaprol is the best option for our patient. It’s given as an injection every 4 to 6 hours. Can you imagine getting a shot, and not a subcutaneous injection like insulin, but a real intramuscular injection like the flu shot every 4 to 6 hours for days and days? Dimercaprol is contraindicated with peanut allergies because the drug is dissolved in peanut oil. It smells like sulfur, ie rotten eggs. Patients do not like it, to put it mildly, but it’s better than death.
The antidote itself has a fascinating history. Its other name is BAL or British anti-Lewisite. Lewisite is an arsine gas, an arsenic containing WWI era chemical weapon, which for some reason, smells like geraniums. The British were concerned it might be used in WWII and developed BAL as an antidote. Lewisite wasn’t used in the war, but it was found to chelate other heavy metals and is now an important antidote.
Back to our patient. His spot arsenic comes back at 100,000 mcg/L. Extremely high, confirming the poisoning and leaving no room for debate. Why do I say that? Because interpretation of arsenic results is complicated. I’m going to touch on this briefly as it’s a point many, including physicians, don’t understand. Doctors love to send heavy-metal testing without understanding the nuances. Elevated arsenic levels are very, very common, arsenic toxicity, you don’t need me to tell you is very rare.
In fact, your arsenic level might be elevated. Mine, too. Are we poisoned? No. Arsenic is ubiquitous in the environment and therefore in food.
Question #4. Which of the following foods are high in arsenic?
A. Fish
B. Rice
C. Beer
D. Barley
E. All of the above
The answer is A, B, and C. Fish, rice and beer and wine all contain arsenic. Eating fish will raise your arsenic level above normal, but you can’t eat enough to develop toxicity like our patient.
Bottom line, random arsenic levels in regular patients aren’t helpful. If for some reason, you really need an accurate level, rarely necessary, the patient has to abstain from fish and rice for two weeks before testing. If there’s arsenic in fish should you stop eating it? Nope, fish and fish oil are good for your cardiovascular health.
The patient is now in the ICU, teetering on the edge of death, getting dimercaperol and supportive care. While we wait to see if he improves with chelation, let’s talk about the mechanism of arsenic toxicity. As with so many life-threatening toxins, it causes energy failure. In this case it inhibits pyruvate dehydrogenase with a resulting decrease in ATP production. It also causes free radical formation, leading to cell damage. It interferes with gluconeogenesis, or glucose production, causing low glucose intracellularly.
Ancient physicians not only new about arsenic’s toxicity, but also it’s therapeutic potential. In ancient China, it was used to treat malaria. Hippocrates used it to treat skin lesions, ulcers and abscesses. Interestingly Paracelsus used it extensively, recording detailed instructions on its production. Remember his famous quote, it’s the dose that determines the poison.
In the 1800s, arsenicals were not only ingested, but inhaled, given as enemas and as vaginal inserts and powders. Personally, I’m surprised anyone exposed to medicine- I use the term loosely here- in the Victorian era survived. Think arsenic enemas are crazy? I did, but apparently, we still have arsenic derived suppositories to treat refractory proctitis.
Research with arsenic for the treatment of syphilis led to the development of the first antibiotic Salvarsan, a play on the words “life-saving arsenic”. Arsenic trioxide is used as a chemotherapeutic agent for refractory leukemia. And a derivative, melarsoprol is used to treat trypanosomiasis, or African sleeping sickness. Interestingly, the pharmaceutical preparation of this drug contains BAL which appears to reduce toxicity for patients without reducing the effectiveness of the drug.
Who poisoned our patient and why is he getting worse despite treatment? Apologies in advance because this episode ends with a cliffhanger. Want to find out? Want to know what the Victorian arsenic poison panic was and what finally slowed it down? You’ll have to listen to the next episode, part 2 to find out because I’ve already talked for too long today. Subscribe so you know when it’s out.
Last question #5, in today’s podcast. What item did ancient Korean kings use to avoid poisoning?
A. Unicorn horns
B. Silver chopsticks
C. Bezoars
D. Ingesting small doses of poison to develop immunity
Follow our Twitter and Instagram feeds both @pickpoison1. Follow and you’ll see the answer when I post it. 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. Remember, 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.