Killer Candy

Want to know what candy can kill you? Though the flavor is so beloved, it was found in King Tut's tomb. And might make camels less thirsty? 

Listen to find out.

Transcript

This is the Pick Your Poison Podcast. I’m Dr JP. ER doctor. Toxicologist, and unapologetic lover of all things poison. 

Want to know what candy can kill you? Though the flavor is so beloved, it was found in King Tut's tomb. And might make camels less thirsty? Stay right here to find out.

This is an interactive story. 

Survival isn't guaranteed. 

What happens next depends on you. Will our patient live or die? 

It's up to you and the choices you make. 

Get ready to chart your course.

Today's episode starts in the emergency department. You pick up the chart of the patient in room 4. She's a 54-year-old woman complaining of high blood pressure. It looks like a pretty quick and easy complaint and the interns and residents are busy with sick patients so you decide to see the patient yourself to expedite her care. 

The patient is sitting comfortably on the bed. Her vital signs are as follows. Blood pressure is 190/80, temperature 98.6 (37 Celsius), heart rate 80 beats per minute, respiratory rate 20 breaths per minute with 100% oxygen saturation on room air.

You ask the patient what's been bothering her. She says her blood pressure has been persistently high for the past week despite taking her blood pressure medicine as previously prescribed. Several weeks ago, her doctor recommended she increase the dose of her amlodipine, a calcium channel blocker, which she has done. Despite this her blood pressure continues to be high, so she decided to come to the emergency department.

You ask about associated symptoms. She reports feeling generally weak but denies other complaints including chest pain, shortness of breath, focal weakness or tingling, or change in urination. No fever, cough or flu complaints No vomiting or diarrhea, in fact she denies all other complaints. She doesn't take any medicines other than the antihypertensive. She denies supplements. She also denies tobacco, alcohol, and drug use.

Question number one: What over-the-counter medicine is the frequent culprit in elevating blood pressure?

A.    Diphenhydramine or Benadryl.

B.     Acetaminophen (i.e. Tylenol or Paracetamol)

C.     Allergy medicine. loratadine or cetirizine (i.e. Claritin and Xyrtec)

D.    Decongestants like psuedoephedrine ie Sudafed.

The answer is D. Decongestants like Sudafed contain sympathomimetic qualities and they can raise your blood pressure. This is why people with high blood pressure are advised to avoid these when they have cold or flu symptoms but they're a pretty common culprit in the emergency department since many people don't know. And while we're on the topic, many cough medicines contain sugar so if you have diabetes you should be sure to take diabetic cough syrup to avoid elevating your blood sugar. Our patient denies any over-the-counter medicines. We've talked about diphenhydramine or Benadryl causing hypertension in the past but this is with anticholinergic toxicity and overdose rather than with therapeutic use.

On exam, she is awake and alert. Her cranial nerves are intact. Her heart and lungs are clear. Her abdomen is soft and non-tender, and she is moving all of her extremities. She seems a little bit weak when you examine her, but it's very subtle and you probably wouldn't notice it if she hadn't specifically complained about it.

Okay so high blood pressure. This is a super super common complaint in the emergency department. People get very worried about their blood pressure. That said, it's very rarely an actual emergency. We always have to explain to patients the difference between acutely high blood pressure causing end organ damage, which we would call a hypertensive emergency, and chronic hypertension. 

High blood pressure is technically a reading over 140/80 with treatment goals of a pressure of 130/80. These goals are to prevent the risks of chronic hypertension, which I'm sure you know, include heart disease, stroke, vision loss, etc. It is important to work with your primary care doctor or your cardiologist, to control your blood pressure on a daily basis.

When people come to the emergency department, they are worried that they've had one or a few high blood pressure readings. It's not, however, what emergency doctors are worried about. We're worried about hypertensive emergencies. 

What's a hypertensive emergency? That's question number two.

A.    Stroke

B.     Heart attack.

C.     Renal failure, i.e. kidney damage

D.    Aneurysm rupture.

E.     All of the above.

The answer is E, all of the above. Hypertensive emergencies are the actual problems occurring from elevated blood pressure whereas treatment of hypertension is about reducing the risk of these bad outcomes. Hypertensive emergencies by definition mean end-organ damage from the high blood pressure I.e. damage to the brain, heart, kidneys, etc.

The very vast majority of patients coming to the ED with an elevated blood pressure reading just need better control (i.e., adjustment of their medicines, improvement in diet to reduce salt, etc.). Often times a history and physical exam is all you need to rule out a hypertensive emergency. Sometimes you may need an EKG or lab work. Occasionally we adjust antihypertensive medicines while the patients are in the emergency department but I have to say most ER doctors don't love doing this because we will not in fact be following the patient to see if their blood pressure improves or to see if they develop side effects etc. In general we prefer to refer them back to the primary care doctor or the cardiologist to make these adjustments as an outpatient.

How do we determine who's actually having a hypertensive emergency?

First and most important are symptoms. If a patient has chest pain with an elevated blood pressure, could it be a heart attack? If they have focal neurological findings with an elevated blood pressure, it could be a stroke. A change in urine output could mean reduced kidney function. Blurry or double vision could mean their eyes have been affected. Sometimes a headache means a hypertensive emergency though it's very common for patients to have headaches and an elevated blood pressure without serious pathology

Our patient is complaining of generalized weakness. This isn't likely related to the high blood pressure because if we were worried about a hypertensive emergency, we'd be worried about a stroke. As I've said a number of times, strokes cause unilateral symptoms not an overall feeling of generalized weakness. We could do a workup to see if something else is happening, causing generalized weakness. Basic labs are useful, checking for anemia and electrolytes disturbances, a urine specimen for urinary tract infection. 

You order some basic labs, the CBC in Chem 7, and a urine specimen, thinking you'll wrap this one up pretty quickly and get back to helping the residents with the sick patients.

An hour later, her results are in. Her urine specimen is unremarkable. Her blood counts are normal, no anemia. But you do find something on the Chem7 to explain the weakness. A potassium of 1.8 mEq (or mmol)/L. This is very, very low, hypokalemia in medical terms. Normal is 3.5-5. The rest of her chem 7 is normal, including her creatinine (i.e., her kidney function). 

All right, you found an explanation for her weakness. Is this potassium caused by the high blood pressure? No. 

What now? We need to replace the potassium. First, you have to make sure you've checked her magnesium. If you didn't all righty because potassium and magnesium are related, and if the magnesium is low, you won't have any success repleting the potassium. Her magnesium is normal. I'd also check an EKG to check for changes related to the hypokalemia.

A couple of minutes later, the tech hands you the EKG. You call the intern over and ask her what she thinks. She looks at it for a few minutes and then says, "What's the patient's potassium?"

You smile and say, "Good job." She says it shows classic changes, including T wave inversion and U waves. U waves are kind of like extra T waves, and they're classically seen with low potassium.

Treating low potassium, at least from an emergency department standpoint, is pretty simple. Simple but not fast. Give the patient potassium. You can do this orally or intravenously, most of the time we do both. Why? Both routes have side effects limiting how much you can give at one time. Oral potassium is very irritating to the stomach, commonly causing nausea and vomiting. Generally, we don't give more than 40 mL equivalents at a time to limit this. If you give more, the patient is more likely to vomit it up than absorb it.

 IV potassium has a different set of side effects, and that's question number 3. Is it?

A.    Stroke.

B.     Seizure

C.     Coma

D.    Cardiac arrest. 

The answer is D, cardiac arrest. IV potassium has to be given very slowly because if you push it quickly, it can cause cardiac arrest. When repleting potassium, we generally give only 10 mL equivalents per hour IV. We usually order 40 mL equivalents, meaning it takes four hours for the patient to get the IV dose. I'd order 40 PO and 40 IV.

What's causing this low potassium did I hear you ask? Good question. 

First, how is the potassium intake, i.e. is the patient eating enough potassium? Most of us encounter plenty of potassium in our regular diets, but if the patient were anorexic, or for some other reason wasn't eating, like dementia or psychosis intake could be the issue. Our patient says she's been eating normally. 

The second question would be, "Is the patient losing potassium?" This can happen via the gastrointestinal tract with vomiting and diarrhea. The patient hasn't had this. In addition, it has to be a copious amount of vomiting/diarrhea, not like a stomach virus for a few days. Diuretics or water pills can certainly cause it, but she hasn't been prescribed those. Long-term steroid use, like prednisone, but again she's not taking that. The kidneys can lose potassium in certain diseases, she doesn't have an elevated kidney function or creatinine.

Nothing is really jumping out at me here. Often, we treat low potassium but don't get to the bottom of the cause in the emergency department. Typically, we replete it and then recommend that the patient follow up as an outpatient for further investigation. 

You return to the room, the patient introduces you to her sister who's sitting at the bedside. You tell them the results and the plan. The patient refuses to stay, saying she needs to take care of her dogs. You tell her this is a dangerously low level that's causing EKG changes, meaning effects on her heart, and could be potentially life-threatening if she leaves. Her sister says she'll text a friend to take care of the dogs. After much back-and-forth, the patient finally agrees to stay.

After she finishes repletion, you repeat the potassium level. You frown at the computer when the repeat level comes back. It's still 1.8. You gave a lot of potassium. It's hard to know exactly how much it will improve the lab test, but in general, we'd expect 80 mEq of potassium to bring her potassium up by 0.8. Meaning she'd be at about 2.5. Safe enough for discharge with a few days of oral potassium until she sees her primary care doctor. Not only has it not come up to a safe level, it hasn't even budged. You scroll through her chart, looking for something that might explain this problem. A shout interrupts your thoughts. "Code Blue, room 4!" 

Uh oh.

You rush into the room, narrowly avoiding being run over by the tech with the code cart. A nurse has her fingers on your patient's neck and says, "no pulse, start CPR." You look at the monitor and see the rhythm. It's ventricular tachycardia, i.e., pulseless V-tach.

Question 4. Is this being caused by the low potassium? 

A.    Yes 

B.     No

The answer is A. yes. It's almost certainly due to the low potassium. This is not good. The patient's sister is backed into a corner. She has a horrified look on her face. You ask her if she wants to stay or leave. She says she'll stay.

What now? First things first, start CPR, get a bag-valve mask to administer oxygen and rescue breaths. What about more potassium? Did I hear you say. Yes, we absolutely need to give more potassium. The question is how fast we can give it. At this point, she's already in cardiac arrest, so that concern is out the window. There's no formula for this, but I'd order another 20 mL equivalent of potassium and tell the nurse to give each 10 mL equivalents over 15 minutes.

Standard ACLS protocol means we should be giving epinephrine. It’s standard of care in cardiac arrest. Why haven't you called for it? Well, epinephrine drives potassium inside the cells, actually lowering the serum potassium level. This is a tough one. It isn't going to help her potassium, which is the reason she's having the cardiac arrest, more than likely. Withholding epinephrine during cardiac arrest is not likely to be in somebody's best interest either. I'd probably give it a few minutes, do a few other things to see if the VT stops. But if it doesn't, I think you have to give the epinephrine.

The intern intubates the patient. You tell her to put an orogastric tube in a tube from the mouth into the stomach, and you order another 40 mEq of oral potassium in liquid form to go down the tube. You could give amiodarone, another anti-dysrhythmic that we can use to treat the fib, unclear if it's helpful if the cause is really low potassium, but there's probably no harm in giving it.

After a few minutes, fortunately, the patient gets a pulse back. The respiratory therapist puts the patient on a ventilator, and you order another 40 ml equivalent of IV potassium. What we need at this point is a consult. I’d get nephrology on the phone stat. Not only are they some of the smartest doctors in medicine, they know a lot about electrolytes.

The nephrologist says he'll be right down. He ordered urine electrolytes to see what's being put out into the urine vs. what's in the serum. He wants an ABG to check the acid-base status as well as phosphate levels.

After a few minutes of scrolling through the chart, he says, “We need the results of those tests to be sure, but hypertension and low potassium typically means mineralocorticoid excess."

What? You say. The term is vaguely familiar. You're pretty sure the last time you heard it was in medical school. 

“Could be hyperaldosteronism.” You do manage to remember that aldosterone comes from the adrenal glands. It can be elevated in some congenital diseases, not likely in her case. Also, if you have a benign tumor in the adrenal glands, it can produce excess aldosterone. If you have narrowing of the blood vessels leading to the kidneys, the same thing can happen.

He orders some hormone levels. Some of these will take days, if not weeks, to come back. He agrees with the aggressive potassium repletion and says to get her admitted to the ICU.

While she's waiting for a bed, you repeat a third potassium level. You're relieved to see it's at least increased to 2 although this is still dangerously low. And not to mention, she's been given a massive amount of potassium. What is happening to it?

You go back into the room. Her sister wipes the tears from her eyes. She picks up a package of candy from the bedside and puts them into her purse, saying, "I guess I’ll take these home. She won’t be able to eat them now.”

“Wait a minute,” you say, "Can I see that?”

She gives you a funny look and says, 'The candy? Sure.' As she passes you the package.

Hmmm. 

You think you know what's happened. I know we have a lot of listeners in the Netherlands and Germany. I bet you've already gotten this one.

Question 5. It's time to pick your poison. Is the candy?

A.                Candy corn.

B.                 Black licorice

C.                 milk chocolate

D.                Swedish Fish

The answer is B. Black licorice. The package says "Dutch licorice drops". You unfold the top and look inside, recoiling from the strong anise smell. You don't remember much from medical school about mineralocorticoids but you do know about black licorice toxicity. It affects the kidneys, causing low potassium, weakness, and, in rare cases, even death.

You rush back out to catch the nephrologist, who's finishing up his consult note. You hold up the bag and he says, " You got it. That's the culprit."

The medicine and emergency medicine residents circle around, asking questions about how licorice caused a cardiac arrest. You're relieved when the nephrologist answers since you have forgotten the mechanism behind this fairly rare and unusual toxin.

The toxic ingredient in black licorice is Glycyrrhizin. Let me clarify Glycyrrhizin is found only in strong black licorice. It's not found in the red licorice we have in the United States, like Twizzlers. Even American black licorice is usually made with anise rather than high concentrations of licorice. You can get strong types here in US, it's usually imported from Europe, often the Netherlands, and Germany. I didn't know before this Episode, there are non-alcoholic pastis-flavored drinks in France which can contain high levels of glycyrrhizin and can cause toxicity with frequent consumption. And that's The other important point. Toxicity occurs with very frequent and long-standing consumption, not from a few bites or a few sips.

The sister says the patient has been buying expensive imported black licorice and eating several bags a day for years. How does licorice cause toxicity? Again, you're relieved the nephrologist is here to answer these questions. He says, “When you eat black licorice, Glycyrrhizin goes inside the kidneys. It inhibits an enzyme preventing the conversion of cortisol to cortisone. Resulting in cortisol accumulation to very high levels and causing something called pseudo-hyperaldosteronism. Cortisol binds to the same receptors as aldosterone and this causes the body to think too much aldosterone is present, which in turn causes the kidneys to retain water. This results in high blood pressure. It also causes the kidneys to lose potassium, excreting it in the urine and resulting in hypokalemia.

Hypertension and hypokalemia, which is exactly what our patient has. It's the reason for the refractory high blood pressure, despite reasonable treatment by her primary care doctor. Symptoms can occur in as little as a few weeks to over months. 

Interestingly susceptibility to glycyrrhizin varies considerably between patients. Women seem to be more sensitive than men. People who are very sensitive can be affected by 100 mg of glycyrrhizic acid (i.e. approximately 50 g of licorice candy), while other people can eat 400 mg without a problem. 

What else happens? You can also see rhabdomyolysis, i.e., muscle breakdown. Paralysis due to severe hypokalemia, even causing respiratory failure. Patients can develop renal failure. Increased blood pressure in the setting of underlying hypertension can result in hypertensive emergencies, including heart failure, hypertensive encephalopathy ie altered mental status, and stroke.

How much licorice is safe? The World Health Organization  says less than 100 mg per day of glycyrrhizic acid. The Dutch Nutrition Information Bureau, has a limit of 200 mg per day. Many countries have advisories recommending avoiding it all together if you have high blood pressure, or other cardiovascular disease, chronic kidney disease, or a history of low potassium. 

Back to our patient. She goes up to the intensive care unit where she's treated with ongoing repletion. They continue to give her potassium liquid down her OG tube as well as intravenously. Obviously the black licorice exposure has been removed, and in a few days, her potassium has stabilized to normal amounts. She is extubated and, fortunately, wakes up without any sequelae, including no brain damage from the cardiac arrest. Once patients stop eating black licorice, we expect their potassium to normalize over a few days to a week or so.

 Black licorice is a common source of exposure, but it's not the only route of toxicity: licorice-flavored drinks, as I mentioned earlier, can be responsible. In some cultures, people enjoy Tea made from licorice root. Particularly in Egypt and often during Ramadan. The amount of glycerin in licorice roots is quite high, and there are several cases of toxicity from frequent consumption of homemade tea. Glycyrrhiza is derived from the ancient Greek term ‘glykos’, meaning sweet, and ‘rhiza’, meaning root. The content of glycyrrhizin in licorice roots varies from 2 to 25%, depending on the species

One interesting correlation I noticed in several published cases of toxicity is that the patient was eating licorice to aid in smoking cessation. They were ingesting large amounts in an attempt to control nicotine cravings.

Licorice is an extremely ancient plant and has been used medicinally for almost as long. The earliest mention we have of the plant is on an Assyrian clay tablet dated to the 7th century BCE. Licorice was commonly used in ancient times as medicine. For cough and bronchitis as well as digestive issues, in Chinese traditional medicine it's thought to have anti-inflammatory properties.

A large amount of licorice was found in King Tut's tomb. Greek armies, including that of Alexander the Great, carried it along, using it to reduce thirst. Arabs give it to their camels as well for the same reason when Crossing the desert. 

In modern times Licorice has been used in some unusual things other than candy. Much of American use is now in tobacco and tobacco products. It has been used in a firefighting foam and insulation as well as in compost to grow mushrooms.

This is a fictional case as are all our cases to protect the innocent. In truth it's unlikely that the cause of this patient's electrolyte disturbance would have been discovered in the emergency department but not until after a lengthy workup in the ICU with nephrology. You'd likely have to wait for the results of 24-hour urine electrolyte specimens as well as plasma hormone levels, like aldosterone, to get to the bottom of the cause.

The last question in today's podcast is the Pop Culture Consult. In what movie did the director have actors drink licorice-based mouthwash to turn their mouths black?

A.    Lord of the Rings.

B.     Game of Thrones

C.     Gladiator

D.    Dune.

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