Explosive Heat
Want to know what chemical used to make explosives is also used for weight loss? What drug was used to keep soldiers warm during WWII? 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 Explosive Heat.
Want to know what chemical used to make explosives is also used for weight loss? What drug was used to keep soldiers warm during WWII? Then stay tuned!
Today's episode starts in the emergency department, in the room of a 19-year-old woman lying on the stretcher and sweating profusely. You immediately notice her skin. It’s bright yellow. Her chart notes the chief complaint is nausea and vomiting and lists her vital signs. Temperature of 102.5, heart rate of 140 beats per minute, blood pressure 75 / 35, respiratory rate 25 breaths per minutes and oxygen saturation 100% on room air.
She says her symptoms started several hours ago. She has malaise and fatigue, feeling generally bad and very tired. The fever and sweating have been ongoing for the same amount of time. She denies cough and cold symptoms, abdominal pain, and urinary complaints. Despite her rapid respiratory rate, she denies shortness of breath and chest pain. She has no other complaints.
On physical exam, she’s markedly thin. The chart says 90 pounds or 41 kilos. She's diaphoretic, sweating profusely. The heart rate is fast but regular, lungs clear to auscultation, abdomen soft and nontender. Muscle tone is normal. The most notable finding is her skin. It's bright yellow, especially on her hands. The whites of her eyes are tinged yellow, called scleral icterus.
This looks like jaundice, caused by elevated bilirubin, a sign of liver and biliary disease. If it’s mildly elevated, the skin is tinged yellow, if the level is high, the skin can be the bright yellow of a radioactive sign. Jaundice and fever together are part of something called Charcot’s triad, suggesting the diagnosis of ascending cholangitis, inflammation or infection of the biliary system, a true emergency. While I’d be concerned, our patient is missing the third symptom - abdominal pain. The emergency department treatment is antibiotics.
So, should we give her antibiotics now, or wait until we have more information? Her vital signs are consistent with sepsis, and it’s quite likely she’s in septic shock. Early treatment with antibiotics is beneficial, so yes. The nurse has already placed an IV and started fluids to help the low blood pressure. In addition to antibiotics, you order tests looking for a source of infection including chest x-ray, a urine specimen, lactate and blood cultures, covid and flu swabs. And of course, liver function tests.
Her blood pressure improves marginally with the IV fluids it's now 81/45. Given her weight of 90 lbs, it’s probably low at baseline, still this isn't much of a pressure. The lab results are finally back. Her white blood cell count is normal, a bit of a surprise since it’s usually elevated in sepsis. That said, people can and often do have infections this abnormality, so let’s move on. Ok, even more surprisingly her liver function tests, including her bilirubin, are normal. In fact, none of the labs are what you expected. You check again to make sure you read the results right, then check to make sure you’re reading the right patient’s chart. Completely normal.
Why is she yellow if she’s not jaundiced? Her white blood cell count and lactate, another test useful in infection, are normal. Is sepsis the right diagnosis?
You go back to the room to check on her and see if you can get some more information. She's sweating even more profusely. For a minute, you think she’s peed on the sheets, then you realize it’s her sweat that’s yellow and now soaking through her gown and the bedsheets. Unfortunately, her mental status has deteriorated, she's lethargic and barely opening her eyes.
You ask her again what happened, she's weak and barely able to respond. Finally, she mumbles weight loss pills, then loses consciousness completely. This is useful information, unfortunately there’s no time to stop and think about it because the nurse repeats her temp is now 105.2 F or 40.7C.
Question #1 What temperature defines emergent hyperthermia in adults?
A. 103F or 39.4 C
B. 104 F or 40C
C. 105F or 40.5C
Answer: B 104 F or 40 C.
In general, when you get a fever, it's a good sign and means your immune system is working to fight off infection. Children can tolerate higher temperatures than adults, up to 105F or 40.5 C without difficulty. In adults we start to get worried at 103° f and above 104 is an emergency.
Why? Your body is made of protein and proteins are heat sensitive. In order to function, proteins are coiled up in very specific shapes. Heat exposure changes the structure and can even cause uncoiling. Think of an egg in a frying pan changing from liquid to solid, this is the result of denatured proteins. In hyperthermia, the body is literally cooking from the inside out, resulting in multisystem organ failure. In lay terms, failure of every single part of your body including heart, liver, kidneys, muscles, and brain. This is where our patient is headed if we don’t intervene immediately.
Every minute counts. There are several options and some debate in the medical literature about the best method for cooling. There are two general categories the first is applying ice, or submersion in an ice bath. The second is cooling with mist and fans. The bottom line, use what you have and try to get the temperature down as quickly as possible. One hospital I worked in still had an old cholera bed, a metal stretcher with a metal tub on the top like an old wash basin. The bottom had a hole with a plug for draining fluids. In the case of cholera, diarrhea. We filled up the tub with ice water and submerged the patients to cool them. Most hospitals don't still have these, instead we use wet sheets and ice packs in the armpits and the groin. Another option, morbid but effective, is to put the patient in a body bag and fill it with ice water. Cooling by evaporation using mist and fans is used at large events like marathons.
The nurses pack the patient’s armpits and groin with ice packs, then cover her with wet sheets. If a fan was available, I’d also blow air on her to evaporate some more heat. You can give cold IV fluids to reduce her temperature and I’d consider this. However, it’s benefit is offset by the high chance it will induce shivering. Obviously, shivering is the body's normal response to cold, using muscle activity to raise the temperature. Shivering works against you in the ER and ICU when you're trying to treat hyperthermia. For now, we've done what we can to treat her, let’s cross our fingers and hope it works.
In the Loco episode we discussed toxicologic causes of hyperthermia. I’ll review here very briefly to avoid repetition. For more details, check out that episode. Malignant hyperthermia, typically caused by anesthetics in the operating room, isn't likely. She doesn’t take any psychiatric medicines and her muscle tone is normal, making neuroleptic malignant syndrome and serotonin syndrome unlikely. Alcohol and benzodiazepine withdrawal are always a consideration but they cause hypertension, high blood pressure, rather than low pressure. What about anticholinergic toxicity from something like diphenhydramine brand name Benadryl or jimson weed? In those cases, the skin should be dry, clearly not the case here. That leaves us with a sympathomimetic overdose like cocaine or meth. Certainly, weight loss occurs with chronic use of those drugs, but again her blood pressure should be high rather than low.
The classic categories of toxicologic hyperthermia aren’t helping. Let’s try another approach and consider the massively huge toxicology topic of weight loss drugs. Humans have wanted to be thinner since at least the dawn of recorded history. Weight loss plans and fad diets have existed for almost as long.
The word diet comes from ancient Greece. The Greeks strove for ideal body types and felt obesity not only represented an imbalanced body, but signaled an imbalanced mind. The Greeks understood dieting and exercise worked. In addition, vomiting was recommended and they often took purgatives to reduce calories. Wealthy Greeks enjoyed feasts lasting for hours and routinely vomited during meals to reduce alcohol intake and allow room to eat more.
True or not, William the Conqueror is often credited with starting fad diets in the 1000s. He was overweight, with people joking he looked like he was about to give birth. Too fat to get on his horse, he went on a liquid diet. Liquid in this case meaning alcohol. He was able to get back on his horse, but according to some accounts suffered an injury to his abdomen from the pommel of his saddle, resulting in his death. Also, he was too large to fit into his tomb and reportedly his body burst after priests attempted to stuff him in.
Not being able to mount your horse appears to be a serious problem for overweight kings historically. King Sancho the first is interesting from a toxicologic standpoint. King of Leon in 958 AD, he was deposed after the nobility assumed he was weak-willed due to his obesity. His grandmother took him to Cordova for treatment by Muslim practitioners, famed at the time for medicine. Interestingly, he was treated with theriac. Theriac is supposedly a universal antidote. It’s inventor King Mithradates of Greece proclaimed it could treat every single venom and poison. Over the years, it’s contained variable mixtures of 40-60 different compounds, was used for all sorts of medical problems and continued to be sold until the late 1800s. After treatment, King Sancho was able to mount his horse and regain his throne. In a modern equivalent, US President William Howard Taft vowed to slim down after getting stuck in the White House bathtub.
The popularity of fad diets hasn’t diminished since. Alcohol and cigarette diets experience periodic resurgences. In the 1920s, John Harvey Kellogg, of cereal fame, prescribed “a two-fronted assault on patients’ alimentary canals, introducing quantities of Bulgarian yogurt at both ends.” That’s right, yogurt enemas. If you thought apple cider vinegar diets started with Beyoncé, think again. Poet Lord Byron apparently attributed his thin, pale physique to vinegar and water diets. Unsubstantiated reports suggest opera singer Maria Callas swallowed a tapeworm for weight loss. If you can imagine it, I guarantee someone has suggested it as a diet. Even eating cotton balls has been suggested to create a sensation of fullness. Unfortunately, they also causes intestinal obstructions.
These are some crazy diets, just to name a few. It brings us to the topic of weight loss drugs. Medical weight loss drugs, not say supplements or gas station weight loss pills. You might think this would be less crazy. Turns out, only marginally so. I love this quote from a paper by Bray and Purnell, “The management of obesity is strewn with misadventures.”
The first real medical trial for a weight loss drug in modern times was thyroid hormone. It works, unfortunately with unwanted side effects of hyperthyroidism and proximal muscle weakness. Patients lost weight, yes, but became too weak to stand up out of a chair.
Next, amphetamines. Basically, like taking cocaine or methamphetamine. Effective for weight loss, but even more than thyroid hormone, the risks far outweigh the benefits. They were removed from the market for use in weight loss.
During my research I came across something I’d never heard of, surprising, because this might be the most toxic combination of ingredients I’ve ever seen. Rainbow pills were popular for weight loss in the 1940-1960s. Ingredients varied, but if I wanted to come up with a toxic concoction, I could hardly have done better myself. They often contained amphetamines, thyroid hormone, diuretics and laxatives, barbiturates, digoxin, steroids and Belladonna, all in the same pill.
Fen-phen the combination of fenfluramine and phentermine worked but caused cardiac valvular disease and was removed from the market.
Over the counter weight loss pills certainly aren’t safer. Phenylpropanolamine or PPA was an over-the-counter ingredient you may remember from the 1980s, in Dexatrim. It caused strokes, especially in young women. Ephedra found in supplements, causes strokes and heart attacks. Both were removed from the market.
You may be noticing a theme, which makes me wonder where we’re headed with Ozempic and the other GLP-1 drugs. Time will tell.
All right so that was a not so short, but still extremely condensed, history of medicine and weight loss drugs. Honestly, we could have an entire series, Pick Your Poison: the weight loss edition. But, our patient isn't doing well, let's return our focus to her and what she may have taken. Tons and tons of toxins cause liver failure. The NIH has a website with entire database called LiverTox dedicated to this topic. Our patient’s bright yellow skin is a main feature of her presentation. We’ve established it isn't from jaundice. If you’re a toxicologist you probably know what it is, because this is a board exam question. The answer is a really fascinating toxin from both modern and historical prospectives.
Question # 2. What toxin causes yellow skin discoloration?
A. Silver
B. Nitrates
C. Ketamine
D. Dinitrophenol
Answer: 2,4-Dinitrophenol, or DNP for short, and incredibly dangerous chemical used for weight loss. You can’t ask if this is what she took because she's now comatose. Instead, you intubate her, put her on a ventilator and call the ICU. The nurse places a temperature sensitive foley catheter into her bladder for continuous temperature monitoring. The ICU resident is excited to take care of a patient with a rare poisoning, until you tell him her temperature is still 105. You both know the odds of her surviving this exposure are low.
What is dinitrophenol? It's a chemical used in dyes, as a wood preservative, pesticide, and herbicide. It’s also used to manufacture of explosives. I don’t know about you, but I don’t need much more information it to know taking it for weight loss probably isn’t going to end well. It’s yellow colored, thus yellow skin, sweat, and even tears. You often see yellow more on the hands from people handling pills or powder. Its toxicity has been known since at least 1916. And yet, people today, right now as we speak, are taking it to lose weight.
The story of dinitrophenol starts in World War I, in munitions factories. In the US, 27 fatal poisonings occurred in munitions workers. In France, 36 fatal deaths were reported from occupational exposure. This number is likely an underestimate according to a publication by Roger Perkins in 1919, it’s a dense but fascinating read. He noted workers came from Senegal in addition to France. The Senegalese were treated by “colonial doctors” unfamiliar with DNP toxicity. Many Senegalese workers who reportedly died of “pneumonia”, were noted to have a high fever and profuse sweating, suggesting misdiagnosis and misclassification death due to DNP toxicity.
Many of the factory workers reported dramatic weight loss. It was known at that time DNP intoxication occurred via skin absorption, oral ingestion and inhalation. It was also noted heavy alcohol drinkers were more susceptible to toxicity. Perkins describes cases as follows: temperatures above 40 with yellow colored sweat. The patients became “frightened and excited”, followed by seizures and death. He also described the rigidity noted immediately after death, like early rigor mortis. In modern times, this is also noted in ventilated patients whose chests are constricted making them difficult to ventilate.
Parker had the following to say about therapeutics. “All attempts to relieve the conditions by increasing the heat output or by giving antithermics have no effect. All that can be done is to try to give the body the means of passing the crisis.” That was 1919. I’m sorry to say, therapeutics haven’t changed much here in 2024. What has helped are occupational interventions like improved ventilation and PPE. Once implemented, occupational death rates dropped dramatically.
Somehow focusing on a weight loss rather than death, Stanford researchers Tainter and Cutting in 1933 noted the potential of dinitrophenol while acknowledging the therapeutic window was razor thin. I really can’t imagine how this conversation unfolded. Look a chemical used in munitions factories during WWI, that killed a lot of workers, it might have great obesity treatment potential? A follow up study a year later reported DNP’s incredible popularity. They estimated 100,000 Americans had been treated with it. The Stanford Clinic alone had given out 1.2 million dinitrophenol pills in a year. The study acknowledged several deaths, but minimized the life-threatening effects and blamed most of its irrefutable toxicity on issues with dosing and non-physician prescribed use, like in supplements.
DNP is toxic to the liver, kidneys and nerves. It causes agranulocytosis, a feared medical condition where the bone marrow stops working, leading to loss of white blood cells and severe susceptibility to infection.
Another significant effect is cataracts. One estimate suggests 25,000 people lost their vision due to dinitrophenol exposure. Many were otherwise healthy young women.
In 1933 the FDA prepared a “American Chamber of Horrors” exhibit, shown at the White House and the Chicago World Fair illustrating dangerous drugs and food additives. DNP was featured. It wasn't until 1938 the FDA had the authority to intervene, removing it from the market. If you want to hear more on this check out my talk about The Elixir of Death on the Toxic History! podcast.
It's not tremendously surprising to me that people risk fad diets for weight loss. It is astonishing this clearly toxic drug continues to resurge in popularity. How did we get from deaths in explosive factory workers during WWI to the 19-year-old in our ER with a classic case of DNP poisoning?
Let’s start with how it works, because that’s what’s driving its popularity. Dinitrophenol is a classic uncoupler of oxidative phosphorylation, so much so, it's used in the lab for research on this topic. Oxidative phosphorylation is a big word referring to the process of energy generation inside your cells. Every cell needs energy to work. The energy needs to be controlled. Otherwise, like a munitions factory gone wrong, the cells could explode from too much energy release or not have enough when required. The ATP molecule is an energy source within cells. ATP is produced is inside mitochondria via the electron transport chain. The electron transport chain uses the passage of hydrogen ions across a membrane to generate ATP, ie energy. DNP is lipid soluble, meaning it can easily cross cell membranes. When it does so inside mitochondria, it brings hydrogen ions along. This disrupts the electron transport chain. Instead of energy becoming ATP, energy is released into the cell and becomes heat. It also means calories are wasted as heat. Another classic uncoupler of oxidative phosphorylation is cyanide.
So, the two main effects of DNP are hyperthermia and weight loss, which brings us back around to the fascinating history of its use. In 1980, a physician, Nicholas Bachynsky started weight loss clinics, generating as much as 10 million dollars in revenue per year. What was in the diet pills? You guessed it DNP. Apparently, he came across DNP while translating documents for the US government.
Question #3. DNP was reportedly given to soldiers from which country to keep them warm during WWII?
A. Russia
B. Germany
C. Japan
D. France
Answer: You guessed it, always a safe guess on this podcast. A. Russia. Bachynsky was translating Russian documents and found it was given to Russian soldiers during World War II to keep them warm. Current reports have numerous mentions users of feeling so hot after DNP they took off all their clothes, opened the windows in the dead of winter, and still continued sweating. No doubt the soldiers were warmer, but they probably paid a heavy price for that comfort. In the late 1980s Bachynsky attracted the attention of the FDA and the IRS and was convicted of numerous crimes including insurance fraud, racketeering, and tax evasion. He lost his license and was sent to prison.
This was not enough to stop him. After his release, he continued using DNP to treat patients in Mexico and Europe, shifting his claims to another therapeutic category strewn with misadventures, cancer, making false claims about what he called intracellular hyperthermia therapy.
You’d think, again, this would be the end of the story, but it takes another twist with the saga continuing from a prison encounter. In prison, Bachynsky met Dan Duchaine, called the “steroid guru” and author of The Underground Steroid Handbook. After Duchaine’s release from prison in the late 1990s, he began promoting DNP as a weight loss agent in the bodybuilding community. Tragically, yet predictably, body builders and young women seeking weight loss died. High-profile stories and prosecutions hit the news along with warnings about its danger.
I’d like to say we’ve heard the last of it, but no. Recently at the gym, I heard yet another story, about a young woman purchasing it on the internet illegally from Mexico for weight loss. Who knows what’s really in weight loss pills you buy online, but it shows the staying power of DNP. Given DNP’s widespread use in manufacturing, it’s easy to obtain on the internet. It’s often marked not for human consumption. When I searched DNP for the podcast, the generative AI in my browser helpfully listed a number of locations from which I could buy it. There are many sources like Reddit threads about DNP and purportedly “safe doses”. The medical research is clear no dose of DNP is safe.
A paper from China highlights just how dangerous DNP is. Factory workers were poisoned in an industrial accident. Family members, including children, who helped to care for those exposed also became ill from dinitrophenol on the skin of the affected patients.
As I mentioned, there is no antidote for dinitrophenol exposure and death results from sudden cardiovascular collapse. Treatment is supportive. External decontamination for skin exposures is critical to reduce ongoing exposure and further absorption of the drug. Treatment for agitation and seizures is benzodiazepines. Cooling, of course to treat hyperthermia.
Back to our patient. You check in on her in the ICU. Her temperature rose to 106F or 41C. The ICU started chilled IV fluids and gave her medicine to try to stop shivering. You’re relived to see her temperature comes down to a safe 101.0 degrees. She develops liver, kidney and muscle problems due to the hyperthermia, but improves and wakes up several days later. She admits to taking DNP for weight loss and is diagnosed with anorexia by psychiatry. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.
Today's pop culture consult and the last question in the podcast. The Sleeping Beauty diet suggested taking sleeping pills to sleep for as many as 20 hours a day for weight loss, theorizing you couldn't eat if you weren’t awake. Also called narcorexia, what celebrity tried this diet?
A. Elvis
B. Marilyn Monroe
C. Judy Garland
D. Elizabeth Taylor
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.
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