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Amyl Nitrite Overdose: Clinical Case and Pearls

Michael Macias

The screen adaptation of S. Thompson's novel, Fear and loathing in Las Vegas, depicts the characters Raoul Duke and Dr. Gonzo using Amyl Nitrite in multiple scenes throughout the movie. 

The screen adaptation of S. Thompson's novel, Fear and loathing in Las Vegas, depicts the characters Raoul Duke and Dr. Gonzo using Amyl Nitrite in multiple scenes throughout the movie. 


This case and pearls are provided by Dr. Andrew Ketterer. Thank you so much for the excellent case! Edited by Michael Macias. 


The Case 

An adult male was wheeled into the emergency department appearing ashen gray with blue highlights. Knowing that this was not common in the expected human color palette there was significant immediate concern. Upon discussion with the patient, he frankly admitted to drinking 2 bottles of amyl nitrite in order to attempt to get high.

The patient was alert and conversational, albeit disorganized. Almost immediately after getting shifted onto a bed he began to vomit copiously, filling the room with a tinny miasma of amyl nitrite. At this point our path was pretty well set: we got the airway stuff set up and our pharmacists dug out some methylene blue.


Amyl Nitrite

Before we get into lab values and treatment for the patient, let's discuss what amyl nitrite is and what we should be concerned about.

Amyl nitrite is part of the alkyl nitrite family and has been used previously in medicine for its vasodilator properties given that it can act as a source of nitric oxide. However it also carries with it psychoactive properties which have led to its recreational use and high abuse potential. Typical positive sensations of amyl nitrite ingestion (usually via inhalation) include excitement and euphoria.  You can mix it into your cocaine to add on an extra duration of your high or increase tactile sensation. It can also be snorted on its own to act as an aphrodisiac (known, apparently, as “poppers”). Other less pleasant physical effects include headache, flushing, tachycardia, a warming sensation, relaxation of involuntary muscle and dizziness.

More concerning, amyl nitrite is one of a list of drugs that cause oxidative stress on red blood cells: among other things, large amounts of this stuff can cause the oxidation of Fe2+ (normal hemoglobin) to Fe3+ (methemoglobin). Methemoglobin shifts the oxygen desaturation curve to the left, meaning that O2 has a harder time dissociating to get to the tissues leading to poor tissue perfusion. Hence in our case the ashen appearance of the gentleman's skin. 


Case update

The patient in our case had a pre-treatment methemoglobin level of 61%. For reference, physiologic levels of MetHb usually hover around 1-2%, and 70% is generally regarded as being incompatible with life.

Fortunately, despite a pulse ox reading of 84% (actual PaO2 155 mmHg), the patient maintained his mental status and we weren’t forced to tube him. Approximately 30 minutes after receiving one weight based dose of methylene blue he began to pink back up and he became a little more coherently conversant. His repeat MetHb had improved to a level of 9%.


Some pearls

  • Sodium nitrite which is in the similar family as amyl nitrite is sometimes used as an antidote for cyanide poisoning (generates methemoglobin which then binds cyanide) though hydroxocobalamin has now become the preferred treatment. 
  • Don't believe your pulse oximeter: The probe functions by using 2 wavelengths of light (red and infrared) to measure the ratio between oxyhemoglobin and deoxyhemoglobin. MetHb absorbs equally at the red and infrared wavelengths used by traditional pulse oximetry, which results in an erroneous SpO2 readout near 85%. Our patient’s actual arterial O2 content was 155 on non-rebreather face mask.
  • Give methylene blue, but don’t overdo it. Methylene blue donates electrons to the NADPH pathway (a minor one for reducing Fe3+ to Fe2+), and allows conversion of methemoglobin back to hemoglobin. However, methylene blue itself can cause methemoglobinemia when given in excess, and if the person also takes SSRIs, SNRIs, or MAOIs it can precipitate serotonin syndrome by reversibly inhibiting monoamine oxidase A. The Illinois Poison Control Center recommends a single dose of methylene blue at 1-2mg/kg over 5 minutes to treat methemoglobinemia. In severe cases such as this one, more than one dose may be required, but this hinges primarily on clinical status (mental status and airway protection), as well as continued resolution of the methemoglobinemia.
  • Make sure to cover your other tox bases. Be sure to be on the lookout for a co-ingestion. In addition to checking MetHb levels every 2 hours, we checked COHb, acetaminophen, salicylate, and alcohol levels. Urine tox screen may help if it would possibly alter your management. We also obtained a liver function panel and coagulation panel (the reason for the latter being that if the person has chronic liver damage the only way you might see an acute change is by new coagulopathy). The reason for all this is that you want to cover all your potentially reversible bases in toxicologic emergencies; it’d be bad news if we treated this guy’s methemoglobinemia only to find out later that he’d also taken a couple bottles of Tylenol and blasted out his liver.

Closure

As it was, this guy improved a lot and was sent up to the MICU for monitoring. He was also extremely pleasant throughout the whole thing, which given how close to death he was is pretty impressive.


References

Faley B and Chase H. “A Case of Severe Amyl Nitrite Induced Methomoglobinemia Managed with Methylene Blue.” J Clin Tox. 2012, 2:4.

Cortazzo J and Lichtman A. “Methemoglobinemia: A review and recommendations for management.” J Card Vasc Anes. August 2014. 28(4): 1055-1059.

Original photo from picture provided by: http://pitch.rs/3-copywriting-mistakes-that-are-driving-your-customers-away/fear-and-loathing-in-las-vegas-fear-and-loathing-in-las-vegas-12935663-1920-1080-2/