Pumped
Want to know what eating meat has to do with doping and drug testing in the Olympics? What medicine to treat asthma in horses is abused by humans for weight loss?
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 Pumped. Want to know what eating meat has to do with doping and drug testing in the Olympics? What medicine to treat asthma in horses is abused by humans for weight loss?
Today's episode starts in the park. On the way to your shift, you’ve stopped into the residency picnic, a potluck celebrating the end of the year. You drop off several pies and grab a hotdog. Your favorite intern introduces you to her boyfriend, a big muscular guy. You’ve heard the other residents say he’s a bodybuilder.
You finish your hotdog and walk toward the gates to exit the park. They are sitting on a bench. He’s breathing heavily and sweating profusely despite the mild weather. You raise an eyebrow. She’s worked with you long enough to know it means what the heck is going on here?
“He’s having chest pain,” she says.
He waves a hand to disagree, but instead clutches his chest.
“I think we need to go to the ER,” she says uncertainly. Not the way any EM intern wants to spend a day off. He’s a fit, muscular 25-year-old man with chest pain. The likelihood this chest pain is really an emergency? Low. The risk of a heart attack or an acute coronary syndrome? Less than 1%. But…. He doesn’t look good.
Maybe it’s a collapsed lung or less emergent, but still painful pericarditis, inflammation of the lining around the heart. A pulmonary embolus is possible, a blood clot in the lungs, if he has risk factors.
You nod in agreement. He should be seen. The hospital is only a few minutes away; you hail a cab for the three of you.
On the way, the intern gives you the history. She says he has no medical problems and doesn't take any medicines. Walking around the park, he developed chest pain. It improved after sitting down. They thought maybe it was indigestion. When he got up to walk back to the party, the chest pain returned, extremely severe. He had shortness of breath, nausea, and was sweating copiously. This time it didn't improve when he sat down.
In the Emergency department, you grab your white coat and log into the computer, waiting for the nurses to triage him. Sitting on the stretcher, he’s still diaphoretic, and rubbing his chest. He’s still having chest pain. On the monitor, his temperature is 98.5, heart rate 130 bpm, blood pressure 105/65, normal but low for a big guy like him. Respiratory rate is 18 and oxygen saturation 100% on room air. You examine him, noting a normal mental status, normal breath sounds bilaterally and other than the rapid heart rate, a normal cardiac exam. Extremity strength is good, no edema. He’s very shaky and tremulous. Otherwise, his exam is normal.
You ask him more questions. This isn’t the first episode of chest pain, he reports two others over the past week, though they were mild and self-limited. He says he’s had generalized weakness which he’d attributed to fatigue from ramping up his workout routine. No cough or flu symptoms, no calf pain or swelling and no recent history of immobilization or long trips.
You ask about family history of heart disease, he no and denies any history of clotting disease in himself or family.
The tech rips off the EKG from the machine and hands it to you. You frown. The intern looks over your shoulder, exclaiming, “What!” The monitor beeps as his heart rate shoots up. She struggles to compose the surprised look on her face into her calm doctor’s face.
What’s on the EKG? When we read an EKG we look at a bunch of different things. First, the rhythm, to see if it’s normal or a dysrhythmia, then the intervals, like the QTc interval we’ve discussed before, checking for evidence of certain toxins, as well as predicting the risk of developing a dysrhythmia. Of course, we check for signs of a heart attack or cardiac ischemia.
Our patient’s EKG shows sinus tachycardia, a basic fast heart rate, not an arrhythmia, which is good. It also shows ST segment depression, which is not good. One of the causes of ST depression is cardiac ischemia, meaning the heart isn’t getting enough blood flow. It doesn’t show an actual heart attack, but if we don’t handle this correctly, it could progress.
What now? He’s sweating more profusely; his eyes don’t leave his girlfriend’s very worried face. Is this a cardiac issue? Or something else putting strain on the heart? We need more information, this is far from a definitive diagnosis. We need a chest Xray to rule out pneumothorax, a collapsed lung, another pulmonary issues. We need labs including a troponin, a marker of cardiac disease. It’s a protein found inside heart muscle. If we can measure it in the bloodstream, it’s because it leaked out from a damaged heart. Pulmonary embolus, or PE, is still on the table. Severe cases do strain the heart. He doesn’t have any risk factors, surgery, immobilization, family history, etc but a rapid heart rate and chest pain are signs, so I’d send a ddimer, which if negative rules it out.
You call the x-ray tech, and the nurse gets the labs. In the meantime, what do we do? He's sitting there, clutching his chest and sweating.
Question #1. What medicine should we give?
A. Aspirin
B. Nitroglycerin
C. Morphine
D. All of the above.
The answer is D. All of the above. We need to get rid of the chest pain. It doesn’t matter how, what matters is it stops. I'd order IV fluids to see if that helps the tachycardia. I’d also repeat the EKG in 10 minutes, to make sure it hasn’t progressed to a heart attack.
You get all those things underway, then ask him more questions. You ask your resident to step out for a minute to screen for drugs of abuse. If someone under 40 has cardiovascular disease, like ischemia, heart attack, or stroke, a very common culprit is sympathomimetics like cocaine and methamphetamine. He says occasional marijuana but nothing else. Is this marijuana? No. It does increase the risk of heart disease, evidence is increasing on this front, but doubtful with occasional use and not in 20-year-olds.
Is he lying about other drugs? Maybe he doesn’t want his girlfriend to know. We’ve noted tachycardic and sweating. Both, elements of the sympathomimetic toxidrome. That said, I doubt it’s cocaine or similar because he should have hypertension, not low blood pressure. The picture certainly doesn't fit with opioid, overdose, or hallucinogens. I don’t think his symptoms are due to a drug of abuse.
You ask what he does for a living, considering an occupational exposure. He says he's a bodybuilder, and your intern says proudly that he's recently gotten enough sponsorship to quit his day job.
Question #2. What drugs are commonly used by bodybuilders?
A. Anabolic steroids
B. Caffeine
C. Diuretics
D. Creatnine
E. All of the above
The answer is E. All of the above. Knowing he’s a bodybuilder opens Pandora's box all they way up when it comes to toxicology. They use tons of substances, legal and illegal, over-the-counter and prescription, supported by research to purely speculative or outright disproven, to improve weight, muscle mass, sleep, blood sugar, and everything else in between. Anything is possible here, but let’s start with common categories.
You don’t need me to tell you steroids would be at the top of any list. They cause things like liver failure and mood swings. They can accelerate cardiovascular disease, but even so unlikely at 25.
Human growth hormone is another common one, causing side effects of joint pain, leg swelling and diabetes. Interestingly carpal tunnel syndrome. Bodybuilders take insulin to build muscle and regulate blood glucose.
Amphetamines cause sympathomimetic syndromes, which we’ve already ruled out. Diuretics, ie water pills are also commonly used. This is to reduce weight, look leaner and also to try to cover up performance enhancing drugs in a urine drug test. Certainly, if you’re dehydrated you will have a low blood pressure and a fast heart rate. But cardiac ischemia is a stretch.
Caffeine is another common substance, especially in your regular over-the-counter workout supplements. It does cause tachycardia as I’m sure you know from having a large coffee, but it increases blood pressure, so again not exactly fitting here. Creatine is very widely used; it doesn’t have a lot of side effects. Occasionally kidney issues, but only in the setting of pre-existing problems.
He denies steroids, and says he does take workout supplements. Just as you start to ask more, you’re called into a bad trauma, a pedestrian struck. After you finish taking care of the critically ill patient, you return to your desk, noting his lab results are back.
His blood sugar is a little high at 300 mg/dL (or 16 mmol/L), of course we don’t do fasting glucoses in the ED, so hard to know what to make of that. Could be abnormal or maybe he just ate a slice of pie at the potluck.
His potassium is low, it's 2.5 mmol/L. Unusual in otherwise healthy person. Low potassium causes muscle weakness, explaining at least that part of his history. Your phone rings, it's the lab with a critical result. His troponin is elevated, in the range of a heart attack. Uh oh.
We classify heart attacks into 2 general types. STEMIS, or ST segment elevation myocardial infarctions, diagnosed on EKG. These patients typically go straight to cardiac catheterization for a stent to open the blocked coronary vessel, and NSTEMIs, nonST elevation MIs, which are diagnosed by elevated troponins on blood work.
This is an NSTEMI. What is causing a heart attack in our 25-year-old bodybuilder? Back at his bedside, you deliver the bad news. You ask about non-prescription drugs and supplements. He admits to creatine, caffeine, vitamins, and protein shakes. We’ve already ruled these out.
For a few minutes all he says is “umm and ahh”. Your intern crosses her arms, glares at him and says, “You better tell us the truth unless you want this to be the end.”
Maybe or maybe not, but you don't contradict her because you do need the truth to treat him appropriately. He admits to one other substance. The low potassium is a big clue.
Question number 3. It’s time to pick your poison. This is an interesting toxin, but not a common one, so it’s a tough question. If you’re a lay person, no shame if you guess wrong. Is it?
A. Thyroid hormone
B. Clenbuterol
C. Alcohol causing alcohol withdrawal
D. Aspirin
Answer: B clenbuterol. If you've never heard of this, don’t worry we’ll discuss it in detail. But first a word about the wrong answers. If you guessed thyroid hormone actually, half credit because it does cause tachycardia and is used by bodybuilders to lose weight and speed up metabolism. However, it doesn't cause low potassium or cardiac ischemia.
Alcohol withdrawal would also be great. He's got a high heart rate and tremulousness, but he should have hypertension and unlike alcohol, withdrawal itself isn’t typically associated with cardiovascular disease. Aspirin causes rapid breathing and acidosis, so that doesn't fit.
Back to clenbuterol, you may not have heard of it, but I bet you know albuterol, medicine in asthma rescue inhalers and breathing treatments. If you've seen anybody take a few puffs on their inhaler, you've seen albuterol. We use it like water in the emergency department for wheezing from asthma, bronchitis, and COPD exacerbations. It’s very safe, but it does have some side effects, making patients tachycardic, anxious, shaky, and tremulous.
Just like our patient. Clenbuterol is in the same class as albuterol, both beta agonists. Back to this in a minute. Albuterol is short-acting, via inhalation it works in minutes and lasts a few hours. Clenbuterol is ingested as a pill or liquid, with a peak effect in 2 to 4 hours and a duration anywhere from 24 to 48 hours and even some reports as long as 72 hours.
Clenbuterol isn’t approved for use in humans in the US, only horses with wheezing, though it is used for humans in the EU. It’s not hard to get ahold of and is abused by bodybuilders to build muscle mass and also by people who want to lose weight. Typical side effects, like albuterol, are tachycardia, anxiety, shakiness and low potassium. We didn’t discuss other lab tests, but an elevated lactate is another clue to diagnosis.
In addition to these effects, clenbuterol can cause a lot of other problems. Part of this is probably dose related. Bodybuilders aren’t taking regular doses, but 5 or 10x recommended amounts. Clenbuterol has caused heart attacks and ischemia in otherwise young healthy people, including a patient as young as 17. Yikes. It can cause seizures, arrythmias, psychosis, and rhabdomyolysis i.e. muscle breakdown.
Clenbuterol is a performance enhancing drug, banned in the Olympics and by WADA, the world anti-doping agency. Question #4. Athletes have blamed positive clenbuterol tests on exposure to contaminants in which of the following?
A. Water
B. Meat
C. Kisses
D. Albuterol inhalers
The answer is B. Meat. It’s really interesting, clenbuterol is the reason athletes are often advised to avoid eating meat before a competition in certain countries.
The US in 1991 and the EU in 1996 banned clenbuterol use in livestock after outbreaks of poisoning where hundreds of people developed toxicity after eating meat. Pigs and cows were fed clenbuterol to increase muscle mass, inadvertently poisoning humans eating the meat. Patients developed tachycardia, agitation, and low potassium.
Several athletes who tested positive for clenbuterol have blamed contaminated meat including Alberto Contador who was stripped of the 2010 Tour de France title after a positive drug test. These cases are always controversial, because it can be in meat, in low quantities in some countries, but is definitely abused as a performance enhancing drug. Before the 2012 Olympics, Chinese athletes were advised not to eat any meat to avoid potential cross-contamination. It's not just athletes, clenbuterol toxicity has occurred after exposure to contaminated cocaine and heroin.
What does clenbuterol do? as I said, it's a beta agonist so it stimulates beta receptors. In the lungs B1 receptors cause bronchodilation, opening up the lung passages, helping breathing in patients with asthma or COPD.
B2 receptor stimulation in muscles increases strength of contraptions and increases muscle growth. B3 receptors in fat cause lipolysis or fat breakdown. Activation of B2 receptors also drives potassium inside cells. So much so, we use albuterol in the hospital to treat high potassium which is life-threatening. Albuterol is powerful enough for an emergency, so you can image how clenbuterol can affect potassium, especially if you regularly take supratherapeutic doses.
Back to our patient. Now we know what’s happening. What do we do to treat him? We have two issues, a heart attack and clenbuterol toxicity. First the heart attack, we’ve given aspirin and nitro already. The good news, he says the chest pain is resolved and he’s no longer diaphoretic. A repeat EKG shows normalization in the ST segments. I’d consult cardiology. They agree with conservative management for now, monitoring symptoms and troponins.
Ok good. Now on to the clenbuterol itself. Is there an antidote? That’s question #5.
A. True
B. False
Answer: B false, there is technically no antidote. But we do have medicines that can treat it. I said it’s a b-agonist. We’ve talked about medicines call b-blockers in the past right? We have lots of b-blockers, and they’re typically used as blood pressure medicines, metoprolol is a common one. You could choose anyone, oral or intravenous. Since he’s having ischemia, I’d go with esmolol, a continuous infusion.
The other class of drugs you can consider is every toxicologist favorite, benzodiazepines. These are sedatives and will help him feel less anxious and jittery. I almost forgot to mention potassium supplementation. I’d definitely replete his K before it gets any lower.
Is there a test for clenbuterol? Yes, but as usual, not one with results in a timely fashion, probably a week or so. Even if he hadn't been honest with us, the symptoms of tachycardia, low blood pressure and low potassium are fairly diagnostic, especially once you rule out other causes.
You admit him to the step-down unit to continue titrating the esmolol drip and monitoring troponins.
The history of performance enhancing drugs and doping is a long and extremely fascinating one, enough for a whole podcast series. I love hearing talks at conferences by WADA toxicologists.
According to some sources, the word doping comes for a Dutch word, dop an alcoholic beverage reportedly consumed by Zulus. Interest in performance enhancing compounds is recorded as far back as ancient Greece when a win in the Olympics was attributed to a diet of dried figs. Since then, just about everything you can thing of has been used including alcohol, hallucinogens, animal hearts and testicles, wine, cocaine, heroin, opium and even strychnine.
Back to our patient. His troponins rise over several hours but plateau the following day. He has no further symptoms and is discharged uneventfully. Your intern, now officially a resident, says he’s promised her not to do anymore performance enhancers other than things like caffeine and creatinine. He plans to transition to social media and YouTube exercise videos to avoid the unhealthy standards of bodybuilding competitions.
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.
Last question in todays podcast is a pop quiz! Do you remember what substance used by bodybuilders is also used to manufacture explosives?
A. Amphetamines
B. Steroids
C. Dinitrophenol
D. Salicylates (ie aspirin)
Listen to the explosive heat or 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. Thank you. Until next time, take care and stay safe.