Fresh Air
What to know what antidote is getting more attention on social media than the poison it treats? What happens if the doctor panics while giving it. Why people are drinking fish tank antifungal cleaner?
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 Air Freshener. What to know what antidote is getting more attention on social media than the poison it treats? What happens if the doctor panics while giving it. Why people are drinking fish tank antifungal cleaner? Listen to find out!
Today's episode starts at a party. Your friend from medical school has rented out a big house for a week at the beach. You've taken a few days off to hang out with old friends and meet new ones. After dinner on Saturday night, you're sitting on the deck, enjoying the ocean breeze and catching up.
Suddenly, there's commotion, then a shout for help. You run inside the house. One of the guests is laying on the couch, sweating. His skin is blue gray in color. There are a lot of doctors at this party, but you're the only Emergency Medicine physician. You look up to see everyone looking at you, waiting for your instructions. You don’t know this man well, he’s the friend of your friend. You do know he was healthy enough to teach you and the others to surf this afternoon.
Question number one. What is the first thing you should do?
A. Call 911.
B. Give him syrup of ipecac
C. Drive him to the hospital immediately
D. Get help upstairs into bed.
The answer is A. call 911. If you said drive him to the hospital yourself, partial credit because in truth this depends on EMS response time. We don’t use ipecac anymore, poisoned patients can aspirate the vomit into their lungs making the situation worse. The patient looks cyanotic, i.e. blue gray skin and I'd be very concerned that his oxygen levels are low. If you put him to bed, uh oh, you might’ve killed the patient.
He looks like he needs oxygen therefore, I’d prefer to have EMS transport him. If you’re in the middle or nowhere or the middle of a natural disaster and you can drive him more quickly than EMS, that’s the better option.
While you wait you ask him what happened. He says he was fine about thirty minutes ago, when he became very dizzy and lightheaded, felt some chest pain, started sweating and thought he was going to pass out. You ask if he feels short of breath, he says no. Which is strange given that he looks cyanotic.
The medics arrive, transfer him to the stretcher and hook him up to the monitor. His vital signs are as follows temperature 98. 6 or 38.9 Celsius. Heart rate 115 bpm, blood pressure 110/70, respiratory rate 20 and oxygen saturation is 84% on room air.
The put an oxygen canula into his nose and give him 2L of o2. His pulse ox doesn’t improve. They turn it up to 4L, click the stretcher into place and wheel him out to the ambulance. Just as they do, he starts convulsing with violent generalized tonic, clonic movements.
This is a seizure.
Good thing you elected to call EMS, rather than drive him yourself. The medics give him a lorazepam, ie Ativan, a benzodiazepine to stop the seizure. They change him to an oxygen face mask to administer 100% oxygen. You note his oxygen saturation still doesn't improve.
What is happening here? It’s not clear. What is clear is needs to be in the ED, not the vacation house. You grab the patient’s husband, and race to your car, following the ambulance. En route you ask his husband about the patient’s past medical history. He says the patient is 34 years old, otherwise healthy and doesn't take any medicines. They did have a few drinks this evening and ate a marijuana edible, but he was perfectly fine. The patient has never had a seizure before, as far as he knows. He’s answering your questions with tears streaming down his face. He asks what happened, you respond with It's too early to know, rather than answer who the hell knows.
In the emergency department, the patient is lethargic, but opens his eyes at the sound of his husband's voice. You’re relived the seizure stopped. The lethargy could be a postictal phase, common after a seizure, or due to the lorazepam. Or due to whatever caused this sudden illness.
In real life, you wouldn't be taking care of him, but this is fiction, so it's up to you to figure out what the heck is happening.
You examine the patient, his heart is fast but otherwise normal, his breaths sounds are equal bilaterally and clear. It’s difficult to get a good neuro exam because he’s lethargic, but he’s moving all extremities and doesn’t have any focal findings. In medical jargon that means we can’t exclude an abnormality, but nothing is obviously wrong.
The nurses of course, repeated vital signs, confirming no fever, a normal blood pressure and the mild tachycardia. Notably, he remains hypoxic ie a low oxygen, despite getting 100% oxygen.
Why? That’s what we have to figure out. Breathing has two parts, ventilation and oxygenation. Ventilation is the process of inhaling and exhaling. We talked about paralytics causing respiratory failure and opioids reducing the drive to breathe in your brain stem. He’s breathing at a normal rate with a good effort. Asthma and bronchitis cause airway narrowing, keeping air from getting in, but his lungs are clear without wheezing, so it’s not this.
Oxygenation is getting oxygen from the air into the blood stream. Congestive heart failure is when your heart can’t pump well, causing reduced blood flow as well as fluid build up in the lungs, resulting in low oxygen. Fluids cause the sound of crackling, which, again, is absent here.
Blood clots, pulmonary emboli, could cause this, but this isn’t a pulmonary podcast, It's a toxicology one. I’ll skip ahead and tell you his chest xray is negative and a CT scan shows no clots and no other lung pathology.
Let's move right ahead to toxins impairing oxygenation. Exposure to carbon dioxide causes asphyxiation. Chlorine gas causes pneumonitis, inflammation of the lungs. Smoke inhalation damages the lungs via many methods depending on the nature of the smoke. Metal fume fever, from welding zinc without proper PPE, is due to inflammation. Hypersensitivity pneumonitis can occur from things like exposure to fungi like aspergillosis.
Lots of drugs cause acute respiratory distress syndrome or ARDS, irritation and inflammation in the lungs. It causes changes on x-ray and more importantly develops over hours, more commonly over days. So this doesn’t fit, either.
These are a lot of interesting toxins with interesting pathophysiology, but we don’t have all day, let me sum it up with the following, very few things cause a low oxygen in of itself without pulmonary edema fluid in the lungs, bronchitis or wheezing, or findings on chest-Xray.
The other element you need for oxygenation is hemoglobin. Hemoglobin inside the red cells are what carry oxygen to tissues. If you don’t have enough hemoglobin, you won’t have enough oxygen. This doesn’t happen with mild anemia, even patients getting blood transfusions typically have normal oxygen saturations.
One problem causing a sudden issue with hemoglobin and oxygenation is hemolytic anemia, or breakdown of your red blood cells. G6PD is an enzyme deficiency. If patients are exposed to an oxidizing agent, like eating fava beans, it can trigger hemolysis. It’s hereditary. Any chance our patient could have previously undiagnosed G6PD and eaten fava beans? Possible, but unlikely to present in adulthood, rather than childhood. We’ll be able to tell on his blood tests.
The nurse adjusts his oxygen mask and pulse ox, but nothing changes. There is one test which I would send immediately and in a nice change from our usual toxicology expectations, is actually a quick test. Even quicker than a blood count and electrolytes. Question #2. What’s the test?
A. A blood gas
B. A ddimer
C. A co-ox, or co-oximetry
The answer is C. We need a co-ox. It will test for oxy and deoxy hemoglobin, carbon monoxide and methemoglobinemia. A blood gas measures the pressure ie levels of oxygen and carbon dioxide in the blood. We’ll get a blood gas with the co-ox and you can use either a venous or arterial specimen. A d-dimer is an inflammatory marker we use for pulmonary embolus risk stratification, which we’ve already ruled out.
Could this be carbon monoxide? Great thought. I’m sure you’ve read about people dying from CO in vacation homes and hotels. It can cause seizures and hypoxia. But, not likely here. Why? Everyone in the house would be sick, including you.
The co-ox is a quick test, it just takes a few minutes to run. His results are as follows: oxy hemoglobin 97%. Carboxyhemoglobin level is 2%, so no carbon monoxide toxicity. His methemoglobinemia level is 42%.
Does this explain his symptoms. Yes. He has methemoglobinemia.
Most toxicologists and many astute EM physicians would’ve guessed this. There are two clues, first, refractory hypoxia. ED patients routinely have hypoxia, low oxygen. Of course, it’s life-threatening, but mostly it gets better with oxygen. Second, his skin color. I just said hypoxia is common, every day I see patients with pulse-oxs in the 80s. Some people with COPD, or emphysema, even live at those levels. None of them are blue. The patients with cyanosis, blue skin, are the patients in cardiac arrest. This color skin is way out of proportion to his oxygen saturation in the 80s.
A quick aside to explain how we measure oxygen saturations with a pulse ox. It works the same way in the hospital or at home if you measured yours during Covid for example. The pulse ox is a colorimetric measure, meaning it measures the wavelength of the blood. Normal oxygenated blood is a certain color corresponding to a certain wavelength. Nail polish can interfere as well as a few other things, but generally it’s a great test.
How can we explain the discrepancy we are seeing on the monitor, reading a low oxygen saturation, but the blood co-ox showing 97% saturation. His problem is that 40% of his hemoglobin has been converted from oxyhemoglobin to methemoglobin. Methemoglobin can’t carry oxygen. In addition, its blue, changing the color and wavelength of the blood. This means, with methemoglobinemia, regardless of the level, the pulse oxy usually registers in the mid 80s.
First what is this problem methemoglobemia? The entire thing is caused by a single electron in the wrong place. In the setting of an oxidizing agent, more on that in a sec, the iron in hemoglobin goes from Fe +2 to Fe +3 because it loses an electron. It becomes methemoglobin. It doesn’t sound like much of a change, but it’s huge because oxygen can no longer bind.
What causes methemoglobinemia?
Local anesthetics are very common, things like lidocaine creams, or benzocaine sprays. If you ever see a few day-old infant with methemoglobinemia, classically dad is a urologist who has been applying copious amounts of lidocaine cream after circumcision. Antibiotics, like dapsone and rifampin, rarely used these days to treat leprosy and tuberculosis respectively. Some antimalarials. You might’ve heard of, or used phenazopyridine, brand name Azo in the US, to help a urinary tract infection. The box says not to use for more than 3 days, due to risk of methemoglobinemia. Mothballs with naphthalene. Anything with nitrates can cause it as well.
Question # 3. Exposure to the following causes methemoglobin in infants?
A. Cow’s milk
B. Honey
C. Well water
D. Juice
Answer: C. If you have an infant with methemoglobinemia, well water used to mix formula is a culprit. Why? Wells can be contaminated with nitrates from fertilizer. Infants are particularly susceptible until about 6 months old because bacteria in their GI tracts converts nitrites into nitrates.
What are the symptoms of methemoglobinemia? There’s a strong correlation with the level. Anyone can have a level of 3% or so. Most patients have no symptoms until about 15 or 20%. You will see blue- gray skin discoloration. With levels from 20 to 50% patients complain of dizziness, shortness of breath, headaches, and weakness. They can pass out. At 50 to 70%, you see altered mental status, seizures, dysrhythmias and death. Above 70% is generally inconsistent with life. There is one caveat to this. If patients have a baseline anemia, they will experience symptoms at lower levels.
Back to our patient. We’ve diagnosed the problem. How do we treat methemoglobinemia? Is there an antidote? Yes, big hint the antidote is getting a lot of social media and press attention lately. Especially in the United States. Question # 4 Is it?
A. B12 or pyridoxine.
B. Methylene blue.
C. Vitamin D
D. Fish oil
Answer: B. The antidote is methylene blue. First, let's talk about as an antidote, Then we'll come back and talk about all the stuff swirling around including became a nootropic.
Methylene blue is FDA approved for one use, as an antidote for methemoglobinemia. It’s very safe and effective. For mild methemoglobinemia, removal of the offending agent is the treatment needed. This generally works for patients with levels of 15-20%.
Levels of 30% or more should definitely be treated. As I said, methylene blue has few side effects, other than blue urine. The dose is 1 to 2 mg/kg over five minutes to reduce pain with injection. Most patients improve immediately. If after 30 to 60 minutes, they haven’t you can repeat the dose. There’s only one big risk, that’s if the doctor or provider panics.
That’s the main route to a bad outcome. What do I mean? Whenever recommending methylene blue, I always take the time to explain at great length what happens during infusion. I’ve already said patients typically have sats in the 80s, I’ve also said the pulse ox is a colorimetric monitor. Methylene blue was originally a dye, you guessed it, blue colored.
When you administer methylene blue, the patient's blood changes color. Specifically, the pulse ox drops, because the monitor thinks the patient has blue, deoxygenated blood. In reality, their oxygenation is improving because you’re getting rid of methemoglobin, putting that electron back where it belongs and allowing oxygen to bind to their now back to normal hemoglobin.
Every single time, I warn the provider about the pulse ox dropping and warn them not to intubate the patient. More than once, I’ve called back to check in and found out the patient was intubated on a ventilator in the ICU.
Now it’s easier said than done to standby, afraid your patient is worsening, and doing nothing. In almost every other case if you stood around watching the pulse ox drop, doing nothing is malpractice. I’ve been at the bedside many times myself, sweating it out. As long as the patient’s clinical status doesn’t worsen, you just have to wait. The real risk with this antidote, isn’t the drug itself, but the providers overreacting.
If the methylene blue doesn't work? Well, you probably have the wrong diagnosis. Someone told me about a case where the patient stayed blue, no one could figure out what was happing. The next day the patient’s father walked into the room. He was also blue. Neither was poisoned, but the family had hereditary methemoglobinemia, due to hemoglobin M genes. It was discovered in a family in Kentucky called the blue Fuges, the result of a very recessive gene. The Fuges were otherwise healthy and most lived well into old age.
Back to our patient. He’s now alert, since the postictal phase and the lorazepam wore off. You order 2 mg per kilo of methylene blue. You warn the nurse and the patient's husband about a transient, and not real pulse ox drop. 15 minutes later, his pulse ox is 79. You clench your hands inside the pockets of your white coat and grit your teeth. It’s hard to stand there, waiting, even when you know better, when your instincts are shouting to get an airway box and a ventilator.
You asked the patient how he's feeling, he says he’s feeling better. And in 45 minutes, he's back to baseline with a pulse ox of 95%. And a urinal full of blue urine.
Methylene blue is FDA approved as an antidote for methemoglobinemia. It’s used off label for vasoplegia, refractory low blood pressure especially during heart bypass surgery, and it’s been used for sepsis, though this has fallen out of favor.
As I mentioned earlier, the antidote has been getting more attention than the toxin recently. It’s been all over social media since Robert Kennedy, Jr was seen in a video with a glass of blue liquid, presumably methylene blue. This started a social media craze with influencers sticking out their blue tongues.
In the arena of so-called wellness influencers it’s been touted as a nootropic. Full disclosure, I had to look up what that meant, it’s a substance purportedly increasing cognitive function. There are a wild number of claims touting methylene blue as a cure for just about everything, including Alzheimer's, memory loss, aging.
We always stick to the facts here on this podcast and none of these claims are proven. You might find some data in a very small study with a few humans, or few rats showing a benefit and just as easily you find other studies with conflicting data showing a lack of effect of methylene blue as a nootropic.
There's evidence it might be useful in depression, though that's far from proven. One of the issues is methylene blue can cause serotonin syndrome in combination with other drugs, particularly SSRIs. Obviously, people with depression are commonly on those medicines, so the risk benefit analysis is not in favor.
What methylene blue definitely does have is antimicrobial activity. Kind of a side note, but really interesting is that many modern pharmaceutical companies, Bayer for example, began as dye companies in the 1800s. Like dying fabric and clothes. Several dyes were noted to have antimicrobial activity and methylene blue was the first to have significant medical use. It kills some bacteria, fungi, and malaria. It was used as an antimalarial and antibacterial, though briefly. Sulfanilamide displaced it becoming the first real antibiotic; it too is derived from an aniline dye.
Interestingly, in the past, methylene blue was used to test milk. If the milk stayed blue, it was bacteria free. If the methylene blue dissolved and the milk once again became white, it meant bacteria were present, kind of cool. Some people ordering methylene blue online in the present day are accidentally consuming fish tank cleaner, its used for its antifungal properties. Consider yourself forewarned, who knows what else is in with the methylene blue if you drink fish tank cleaner.
All right so we know that our patient has met hemoglobinemia, we've successfully treated him with methylene blue. Will he require additional doses and will his symptoms come back? Well, in order to answer that question we need to know what caused it. If he was exposed to something with a long half-life, it could come back. Dapsone, and antibiotic we used to use for leprosy, and occasionally use now, doesn’t typically cause high levels of methemoglobinemia, but can last for several days even after cessation.
The real question now is how our patient developed methemoglobinemia.
You step out to deal with some pressing issues on other patients. Shortly thereafter the nurse calls you back into the room. The patient sheepishly says he took something he bought in a gas station. Uh oh. We had a whole episode on gas station medicine and even so we only scratched the surface.
Question # 5. Time to pick your poison. The toxin was:
A. Kava kava
B. Kratom
C. Anabolic steroids
D. Poppers
Answer: D poppers. He says he picked up a bottle of Rush. If you grew up in the ‘90s you probably know it’s one of the names poppers is sold under. The actual ingredients vary, as with most unsupervised gas station preparations. They typically contain a nitrate. The composition varies regionally and over time with drug enforcement and legal issues. Amyl nitrate was the most common, in the US this was banned, now butyl nitrate is common. It’s the nitrate that acts as an oxidizing agent, causing the shift from hemoglobin to methemoglobin.
In the US, and in other places, they exist in a legal grey zone. It’s legal to use and sell them as air fresheners, liquid incense, nail polish remover and shoe cleaner. Despite this fact, they are almost never used for those reasons.
They do have a very strong, distinctive smell. Typically, a bottle is opened and the nitrate diffuses into the air in a nightclub or a party. Why? Users report feelings of relaxation and euphoria without any true altered mental status like other drugs. Another big draw is they cause smooth muscle relaxation, including sphincter relaxation facilitating, shall we say, the party atmosphere.
You find this information surprising, you were there, and didn’t smell anything other than the ocean, and certainly weren’t affected. Sure you were sitting outside, but should’ve smelled something when you went inside to help. Also, he was very sick with a seizure and a high level. I’ve seen tons of patients with mild symptoms and mild methemoglobinemia after inhaling it a party, most are observed and discharged after a few hours. Why was his level so high, and why is his husband, who was in the same room as him totally fine?
He says it was a small liquid bottle, about the size of an energy shot, labeled Rush. After a bit more discussion the patient says wait, aerosolized?
Now you have a good guess as to what happened. That's question number 6.
A. The patient was too close to the bottle.
B. He drank it
C. He injected it
The answer is B. He was unaware the typical use is aerosolization. It looked like an energy shot so he drank it. Which explains why his level was so high and everyone else was fine.
Poppers have a long history of use; amyl nitrate was discovered in the 1800s and initially used to treat angina. At the time, it came in an ampule that had to be popped open, thus the name. Even in modern times, amyl nitrate is still in ampules. We talked about cyanide toxicity a few episodes ago and I talked about the old antidote kit, which was a three-step process. The first step was amyl nitrate in an ampule, meant to be popped open and waved under the patient’s nose will you obtained IV access for the other 2 steps. I've seen a ton of cyanide antidote kits open for teaching residents and fellows. I think I’ve seen one amyl nitrate ampule; the others were all suspiciously missing.
Poppers were popular with men having sex with men in the 1970s and 80s because of the relaxation aspect. They became popular again in the 1990s at raves, and are currently having another resurgence.
Our patient thought it might be fun to try a popper for recreational reasons, but unfortunately didn't read the instructions, resulting in a night spent in the hospital, rather than a relaxing evening on the beach.
Fortunately, he makes a full recovery with no sequela, and all of you are able to get back and enjoy what remains of the weekend. This is a fictional case, as are all our cases, but based on real poisonings.
Last question in today’s podcast. Poppers were blamed, falsely, and bizarrely I might add, for what epidemic?
A. Covid
B. AIDS
C. Ebola
D. Swine flu
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.