Case:
A 23 year old female, with a history of well-controlled depression on sertraline and no other problems. She had some dysuria recently and was prescribed a few meds to help out; she can't remember what they are.
CC: "I'm blue"
Initial impressions: A depressed person saying that they are "blue" can mean they are emotionally blue or it can open the door to all of the crazy poisons. A blue patient is one that could potentially be poisoned with:
Methanol or ethylene glycol--coloring additives and dyes, especially when it comes to methanol
Flame colorant crystals and other copper containing products (e.g. plant killers)
Analine dye
Gun-bluing solution containing selenious acid (insanely lethal)
Methemoglomenima-associated drugs including "poppers" (amyl and butyl nitrite)
Drunk college kid who thought blue-curaçao was a good idea
Someone that OD'd on handfuls of Tylenol PM
Partly-treated old-school cyanide poisoned patients (e.g. those treated with sodium nitrite or amyl nitrite, intentionally)
VS: HR 118, BP 102/58, RR 24, SpO2 86% on 2L initially, same 86% on 15L, eventually MD turns O2 supply to flush rate
Physical exam: Normal mentation, acrocyanosis and peripheral cyanosis
Thoughts: This patient is tachypneic, tachycardic, with an O2 sat on co-oximetry that remains relatively fixed despite an increasing amount of supplied hospital oxygen. nasal canula can reliably deliver 5-6LPM before you start getting an uncomfortable patient; however a NRB mask can head way north of that without much interference. Don't forget about flush rate oxygen--a hospital's maximum supply rate--which is well above 15. Most of those Christmas-tree green monitors appear to stop at 15 LPM, but keep turning clockwise and you can deliver gallons and gallons more of oxygen per minute to your patient if you're motivated enough.
Most importantly: The patient has respiratory distress and "monitor" hypoxia in the face of preserved mental status and functioning equipment. There is cyanosis compatible with impaired distal and even central oxygenation. The monitor reading is marginally helpful, concerning, and should prompt immediate action.
The differential for this patient becomes exceptionally small--a large acquired physiologic shunt is occurring. Other causes of hypoxemia including COVID, PE, PTX, aspiration, etc. do not present with the same combination of preserved mental status and cyanosis. Get more history, fast, and start thinking about treatment.
Additional history: The patient reports a recent UTI, treated with Bactrim and Pyridium (trimethoprim-sulfamethoxazole and phenazopyridine). While TMP-SMX is a great drug in many ways, it is notorious for its association with TEN-SJS...that's not our problem here though. What about phenazopyridine? This "anti-bladder-spasm" drug has a handful of nucleophiolic-nitrogens in there (cue any drug with the -azo or -hydraz- or -nitrite sounds associated) and can precipitate a methemoglominemic crisis way more easily than you're probably aware.
NEXT STEPS:
Recognize methemoglobinemia before the lab tells you (don't forget that you might have to order a special blood gas)
Immediately order at least 1 mg/kg of methylene blue while you're placing the patient on supplemental oxygen
Appreciate that intubating a methemoglobinemic patient with a persistent SpO2 of 82-87% will do nothing to fix the monitor, or your concerns, so don't waste your time intubating
Disposition:
Admit any patient treated for methemoglobinemia for monitoring and evaluation. Few patients need >1 dose of methylene blue, but some may even need infusions (e.g. massive suicidal aniline dye ingestion)--you shouldn't ever have to decide that).
Take Home Points:
Azo, Pyridium, and similar "bladder pain" drugs are magic for the pain associated with UTI. Unfortunately, rarely, they are life threatening. You have to get this history within a matter of minutes of a patient arriving. You will not have labs. You will only have a semi-blue patient and bad vital signs before you must initiate treatment. Know your drugs, understand that a monitor reading of 82-88% is often associated with methemoglobinemia, and get ready to act.
References:
Wills BK, Cumpston KL, Downs JW, Rose SR. Causative Agents in Clinically Significant Methemoglobinemia: A National Poison Data System Study. Am J Ther. 2020 Dec 29;Publish Ahead of Print. doi: 10.1097/MJT.0000000000001277. Epub ahead of print. PMID: 33416248.
Jeffery WH, Zelicoff AP, Hardy WR. Acquired methemoglobinemia and hemolytic anemia after usual doses of phenazopyridine. Drug Intell Clin Pharm. 1982 Feb;16(2):157-9. doi: 10.1177/106002808201600212. PMID: 7075467.
Tox & Hound. Tox and Hound – Fellow Friday – Methylene Blue Infusions. EMCrit Blog. Published on June 22, 2018. Accessed on January 15th 2021. Available at [https://emcrit.org/toxhound/refractory-methemoglobinemia/ ].
For more info on Pulseoxology in Methemoglobinemia: https://twitter.com/samstellpflug/status/1307086696765444096?s=21
Written by: Dr. Joseph Kennedy
Joe is a senior fellow in medical toxicology at the Toxikon Consortium in Chicago and alumni of the Harvard-affiliated BWH/MGH Emergency Medicine Residency in Boston. He is most passionate about resident and student education in toxicology and related disciplines.
Twitter: @JoeKennedyEM