Hey Dr Bernard here. This throat numbing spray
is medicine. There’s a label on the bottle required by law telling you how to take it, and there’s
a warning on that label, saying what can happen if you take too much. Like this. That’s
a lot of sprays. Just be careful when using it. A Man Swallowed 1 Bottle Of Throat Numbing Spray While Eating Spicy Food. This
Is What Happened To His Brain. RJ is a 21 year old man, presenting to the
emergency room with shortness of breath, nausea, and cyanosis. His face, especially
his lips were a pale blue color. A few hours earlier, RJ was eating
spicy food with his friends. One of his roommates had recently started working
at a hot sauce store, and wanted to host a little contest amongst friends to see
who could handle the spiciest spice. RJ was someone who just couldn’t be topped. He
was that guy in the house who always had to argue with everyone and he had to show everyone up. He
looked online for ways to handle extreme spice and came across throat numbing spray, usually used
to treat sore throat and canker sores. He went to the store, found a bottle, tried one spray in
his mouth to understand what he was working with, and he determined— it was time for him
to outshine his roommates, again. Later that week, on The Day Of The Spice, the friends were ready to have some delicious
chicken wings. One of the roommates dropped out quick because they didnt like spicy
foods, they just wanted to taste flavor and enjoy what they ate. But everyone else
knew that they wanted to show each other up. RJ hid the throat numbing spray underneath his
napkin, occasionally sneaking in a spray here and there while everyone else was eating. At first,
he would make it look like he was wiping his mouth when really, he was pumping that spray. The
sauces that they moved on to got spicier. Some of the friends were having trouble handling it, but
RJ wasn’t going to back down. He wasnt going to admit that this was spicier than he could handle.
He felt like the sprays were starting to not do anything, and the bottle was kinda tall under the
napkin, maybe looking kind of obvious. He started to suspect that the others were catching on to
him as he unscrewed the bottle of throat numbing spray so he could take a couple of swigs. But
accidentally, he spilled the bottle into his mouth and some it started dripping down his chin. In an
effort to not make it obvious to his friends that he was adding a little help on the side to handle
the spice, he swallowed what was in his mouth. RJ felt like his tongue was too big for his mouth.
He could bite down on it and feel nothing. But then he felt like his head was pounding. He could
feel his heart beating in his neck as the air coming out of his nose felt warmer than normal.
One of the friends suspected something was wrong, but they just didnt know what. He called RJ out
and said, “Check out Papa Smurf over here” as everyone noticed that RJ was blue in in the
face. The throat numbing spray that he was hiding was blue and he some of it was dripping
off his chin. Panicked, thinking that everyone knew what he was doing, RJ got up and quickly
ran to the bathroom. But the moment he got up, his field of vision turned dark. In the
bathroom now, RJ was gasping for air. The sounds in his ears couldn’t make any sense to
him. One of the friends found the empty bottle of throat numbing spray on RJ’s seat and
realized what he had been doing. At first, they found it hilarious. But when they looked
closer at the bottle, they saw a warning to seek immediate medical attention if blue colored
skin develops during the use of this product. And when RJ wouldn’t come out of the bathroom, they
went in and saw his complexion an even paler blue color. He was laying down on the floor, as they
drive him to the emergency room where we are now. Immediately, medical staff notice RJ’s
cyanosis. Cyan from Ancient Greek referring to the blue-green color and -osis meaning abnormal
state. His face his lips, and his nail beds were a bluish green color, indicating that there’s
some lack of oxygen in RJ’s blood. They quickly give him supplemental oxygen in order to remedy
this. This throat numbing spray that RJ dumped into his mouth is the same cyan color that his
complexion is now, but, he spilled some of it on to the skin of his face. It’s possible that
some of the food coloring dyed his lips blue, and that nothing at all is wrong with RJ meaning
that maybe that oxygen isn’t going to do anything. But as the time passes, it becomes clear that that
oxygen isn’t going to do anything, but there’s definitely something wrong. The oxygen doesn’t
change the color of his complexion. Even worse, he’s starting to become unresponsive, meaning that
something is happening to his brain. When he presented to the emergency room, they had put
a pulse oximeter on his finger in order to check oxygen saturation in his blood, that is the
measure of how much his hemoglobin, that is the protein in red blood cells that’s supposed to
carry oxygen, is actually carrying oxygen. The pulse oximeter shines a light on one end,
and measures how much remaining light is received on the opposite end to determine that
percentage of oxygen absorbed by his red blood cells. If they’ve been giving him oxygen,
but he’s still blue, and the pulse oximeter is saying that his hemoglobin isn’t carrying
a lot of oxygen, and it’s clear now that his brain is shutting down because it’s not getting
enough oxygen, then what could be happening? The medical team draws some blood from RJ’s
arteries to test. And finds that huge amounts of oxygen are in his blood. This should make
sense. The oxygen that RJ is receiving is going into his lungs, and put into the blood that’s
coming from his heart. This oxygenated blood then flows back to the heart where it’s pumped
out to the rest of the body through the arteries, which is where the medical team drew his
blood. But if all of this is happening, WHY is the pulse oximeter saying
that RJ’s oxygen saturation is low? And more importantly, why is
he still blue and gasping for air? Red blood cells are supposed to carry oxygen.
They do this through a protein called hemoglobin, which contains iron, and that’s what carries
the oxygen. If the arterial blood that the medical team collected from RJ shows that he
has a large pressure of oxygen in his blood, but the pulse oximeter is showing there isn’t
much oxygen attached to his blood cells, then it means that oxygen is in the blood, but
for some reason his red blood cells can’t hold on to that oxygen. And if iron in hemoglobin is
supposed to carry that oxygen in normal function, then this is where RJ’s problem is. This
methemoglobinemia, met from meta in this case referring to between, or a kind of
altered state while retaining some structure and characteristic of the original but being
different in a very important aspect of function, hemoglobin being the protein that holds on
to oxygen, and -emia meaning presence in blood. An altered hemoglobin presence
in blood, but why is this happening? The active ingredient in the spray that RJ used is
benzocaine. The -caine suffix in the name denotes a local anesthetic, meaning that it’s a medicine
that’s supposed to numb the area to where it’s applied. The nerves rely on sending electrical
signals to the brain for the sensation of pain, but benzocaine generally dampens that electrical
signal so that the pain sensation isn’t sent. This happens at regular doses, which for
this throat numbing spray is one pump, that’s spit out after leaving it in the mouth
for a minute. But that’s not even close to the amount that RJ took and put inside his
body. And at doses like the one he took, the chemical structure of benzocaine
explains everything happening to RJ. We’re familiar with metallic iron. When metals
are used for normal function in the human body, they’re not in their solid
metal form, they’re ions, meaning that they are electrically
charged. The problem with iron, is that it can have different electrical charges.
This is why it’s special, but why does it do that? Electrical charges on elements are because of
changes in how many electrons are on the atom. If there’s more electrons than normal, then that
ion is negative. If there’s less electrons than normal, then that ion is positive. Normal is
dictated by the number of protons in the atom, which are positively charged, so when the number
of electrons equals the number of protons, the atom isn’t charged at all. Nature has a
tendency towards stability, in this case referring to less energy. Electrons on atoms are laid out
in energy levels. The larger the element, the more energy it has, and that means it can become
more reactive, because it can release, or wants to release that energy and react with something to
become more stable. The reason why iron is special is because of exactly how many protons it has,
and how energy levels are arranged in nature. The layout of the periodic table
of elements tells us the energy levels of every single element. Each of the
columns on the left and right denote groups, and members of each group tend to exhibit some
similarities with each other, while going along a row denotes an incremental increase in protons,
and elements will tend to behave differently as you count up. Iron is the first of its group,
but the row that it’s in is called the Transition Metals. As we count upwards on Iron’s energy
levels, nature says we can remove 2 electrons, and iron can be stable, because removing those
2 electrons eliminates its highest energy level, giving some stability to the ion. The interesting
thing about iron 2+ in hemoglobin, is that it’s responsible for carrying oxygen and delivering it
to tissues and organs. However, the reason it can bind oxygen is because it still has some degree
of instability, and the electron placement of Iron 2+ tells us that further stability can be
achieved when one more electron is removed, because at the remaining highest energy level, the
presence of a 6th electron in that energy orbital, as is the case for Iron 2+, provides some
opposition. We see this play out in daily life. When rust forms, it’s iron coming into contact
with oxygen and water, that pulls away electrons from the metal and forms hydrated Iron 3 oxide.
While Iron 3+ is more stable— in hemoglobin, its presence means that that hemoglobin
can no longer carry oxygen. Actually, while regular hemoglobin is holding on
to oxygen, the Iron 2 becomes Iron 3, plus oxygen, and becomes Iron 2 again when it
lets go of the oxygen. But as this methemoglobin circulates around in RJ’s body, none of his
organs can get oxygen because his blood cells cant transport it in, as they start to shut down.
His brain is starving of oxygen as he becomes unconscious and it starts to shut down. But
what does this have to do with benzocaine spray? RJ sprayed too much, when he was still only
spraying. The oral mucosa is highly vascularized, meaning that lots of blood is flowing
through. So he was getting benzocaine absorbing into his blood here, and he
was swallowing the sprays. But then, he accidentally dumped the bottle in his
mouth and swallowed even more. The benzocaine spray then went into his stomach, absorbed
from his small intestines into his liver, where it was metabolized, or broken down,
adding even more to the amount in his body. One goal of liver metabolism is to make the
chemical more water soluble meaning it can dissolve in water, so it can concentrate in the
urine and be eliminated from the body. This is called making the chemical more hydrophilic. Hydro
meaning water and philic meaning affinity for. Water is made of oxygen and hydrogen, so adding
oxygens to a chemical in this way, should increase hydrophilicity, but, for benzocaine, doing this
brings us back to the problem of stability. We already established that electrons play a
role in the stability of iron. When benzocaine is metabolized, one of the resulting chemicals
that happens to be hydrophilic, is a phenyl hydroxyl amine. The electrons in this molecule
are delocalized, meaning that they are distributed among the structure, a little different from
how elemental iron places them on energy levels. Phenyl hydroxyl amine is hydrophilic, but it isn’t
stable. It has an extra electron it wants to get rid of to establish stability, therefore making
it reactive. The human body has an abundance of oxygen, so Phenyl hydroxyl amine gives its extra
electron to oxygen and becomes nitrosobenzene, while that receiving oxygen becomes superoxide,
an oxygen with an extra electron. Superoxide is reactive meaning it isn’t stable, so the body
tries to handle this by reacting it with water, but that creates hydrogen peroxide, which is an unstable chemical that takes electrons to become stable. And if hydrogen peroxide is in the blood, an easy target to take electrons from, is Iron 2+ in hemoglobin. This brings us to an idea called equilibrium.
The nitrosobenzene from Phenyl hydroxyl amine produced by the metabolism of benzocaine, is also
unstable. It pulls electrons from elsewhere in the body to become phenyl hydroxyl amine again.
The two of these species, exist together, endlessly cycling between one another, shuffling
electrons around and creating massive amounts of superoxide, and exerting heavy oxidant
stress, reacting with iron 2+ in the blood, turning significant parts of RJ’s hemoglobin
into methemoglobin, incapable of transporting any oxygen throughout the body, despite the
direct administration of oxygen into his lungs. This mechanism of oxidant attack in the blood
happens with several different chemicals, when they are put in to the body, all
of which result in methemoglobinemia, and can cause all the organs to
shut down due to lack of oxygen. In the hospital, the medical team already
picked up on what was happening. They may not have known that benzocaine was the cause
at first, but the clues to methemoglobinemia were all there. RJ’s blue face and lips and
gasping for air. The low oxygen saturation on pulse oximetry when supplemental oxygen
was being given. The high oxygen pressure during the blood test, and the chocolate
appearance of the blood when it was drawn, not being a bright red like normal.
If RJ’s problem is electrons being extracted from the iron in his blood, how
is one supposed to replace those electrons? This brings us back to equilibrium. Methemoglobin
exists in normal function, it’s just that our bodies can easily add the extra electron to Iron
3+ to make it Iron 2+, so there isn’t normally a lot of methemoglobin. But when an endless
cycling of phenyl hydroxyl amine from a huge ingestion of benzocaine keeps creating stress,
the body’s mechanism to reduce Iron 3 is quickly overwhelmed. However, there’s another approach
the body can use, it just needs an intermediate to help carry the electrons around. And ironically,
as RJ’s skin and lips are blue, the antidote that will replace the electrons in the iron in
his blood, is a dye called methylene blue. The medical team noted RJ’s methemoglobinemia,
but it was one of the friends who showed staff the bottle of benzocaine throat numbing spray
that they thought he drank. The medication label has a clear warning on the back to not misuse
it. And all of this prompted the medical team to start methylene blue, when they gathered the
information they needed to know. And very quickly, an improvement was found in RJ’s cyanosis.
But more time was needed to observe him in the hospital, because while methylene blue
was indicated in his case because of how severe his methemoglobinemia was, it isn’t
without risk, and RJ took enough benzocaine, that just one dose of methylene
blue probably isn’t going to be enough. Misusing throat numbing spray isn’t new.
It’s not hard to find videos of people doing it. Not all throat numbing sprays
are made the same. Some have different active ingredients that aren’t benzocaine,
and thus, may not cause methemoglobinemia, although they could cause other problems when misused.
Benzocaine is also found in some cough drops, and that has the same methemoglobinemia warning,
which if you look, the US FDA has issued warnings several times throughout the years about this.
Also because benzocaine is a topical anesthetic, there could be misuse in other sensitive parts
of the body. There is no limit to what you can choose to imagine here. Medical literature
has documented risks with benzocaine spray, sometimes during endoscopic procedures, and
I remember a time in the mid 2010’s when the spray was something hard to get in the hospital in
part because of this problem of methemoglobinemia. Throat numbing spray can be helpful when you have
the common ailments of cold, flu, sore throat, canker sores, not to eat more spicy foods than
your friends. Please be careful because this dosage form can be easy to want to take more,
the directions for use are right on the label. Last point, the antidote methylene blue is used
here because RJ had an active poisoning. If you don’t have an acute illness, or a
diagnosed pathological condition, if you don’t need to put it in your body, don’t
put it in your body. As RJ was monitored in the hospital he needed a bit more methylene
blue. But finally as the days passed and he was watched closely by the medical
team, he was discharged from the hospital as he learned a lesson about not needing to
argue and show up his friends all the time, and about not misusing throat numbing spray
as he was able to make a full recovery. Thanks so much for watching. Take
care of yourself. And be well.
This is probably the single best explanation as to the chemistry of methemoglobinemia, which has clinical relevance to EMS. The electron "shuffle" from oxidant attack may result from exposure to a broad range of chemicals, including nitrates and nitrites (including salts used to cure meats), *caine anaesthetics, amyl nitrate "poppers," nitric oxide, and dapsone (among others), as well as certain hereditary methemoglobinemias such as cytochrome b5 reductase deficiency.
Arterial blood draws (does anyone do this in prehospital care?) may reveal chocolate brown blood.
An interesting video with a great explanation as to the mechanism.
This guy makes so incredible good videos, i love them.
I had a case recently after intentional sodium nitrate overdose. It was interesting the watch the response during and after methylene blue. From hypotensive and crazy low pulse ox (false read) and can’t sit on their own to wnl vitals and walking in less than an hour.
Similar case here that does a nice job showing the cyanosis and subsequent improvement