Baylor University Medical Center Proceedings April 2014, Volume 27, Number 2 | Page 61

Figure 2. Hemoglobin extinction curves. Pulse oximetry uses the 660 and 940
nm wavelengths. As carboxyhemoglobin and oxyhemoglobin absorb equally at
660 nm, they both read the same oxygen saturation on a conventional pulse
oximeter. From Huford W, Kratz A (2). Copyright © 2004 Massachusetts Medical
Society. Reprinted with permission from Massachusetts Medical Society.

equates to an oxygen saturation of 85% (5). Therefore, the pulse
oximeter will display an oxygen saturation of approximately
85% regardless of the patient’s real oxygenation status.
Newer oximeters called co-oximeters measure absorption at
multiple wavelengths, which circumvents the issue seen with
traditional pulse oximeters. Co-oximeters will determine the
percentage of hemoglobin converted to methemoglobin and
carboxyhemoglobin and also will provide an accurate estimate
of the true oxygen saturation state of hemoglobin. However,
these co-oximeters are not widely used (5).
Most cases of methemoglobinemia will resolve within 24
to 36 hours. In severe cases, particularly when the methemoglobin blood level is above 30%, prompt treatment with methylene blue is advised. Methylene blue is quickly reduced by
NADPH methemoglobin reductase to leukomethylene blue,
which then reduces methemoglobin to hemoglobin. This is
called the methylene blue rescue pathway. This rescue pathway
relies on an intact glucose-6-phosphate dehydrogenase (G6PD)
system. In the rare event that the patient’s status worsens after

April 2014

methylene blue administration, G6PD deficiency should be
strongly suspected.
Benzocaine is still a widely used anesthetic. There are several
different formulations, the spray form being the most commonly used. Benzocaine sprays are marketed under different
brand names such as Hurricaine, Cetacaine, Exactacain, and
Topex (1). The benzocaine concentration in these formulations
ranges from 14% to 20%. The benzocaine dosage that can produce methemoglobinemia in adults has been estimated to be
approximately 300 mg, with initial onset of symptoms within
20 to 60 minutes.
The patient presented was exposed to benzocaine during
the second emergent intubation. It is unknown whether the
anesthetic utilized in the first intubation included benzocaine.
However, the benzocaine was administered to a mucosa that
was likely traumatized during the first intubation, potentially increasing its absorption and causing a greater oxidative
burden.
This patient likely had a gastrointestinal perforation from
her prior episode of acute appendicitis. After the second intubation, it was difficult to wean her off the ventilator. ABG analysis
showed her methemoglobin level rising to 45%. The methemoglobin level quickly declined over a period of 2.5 hours after
receiving methylene blue. Unfortunately, the patient developed
significant hemodynamic instability likely due to multiple factors, ultimately developed multiorgan failure and anoxic brain
injury, and subsequently died.
1.

2.
3.

4.
5.

US Food and Drug Administration. FDA continues to receive reports
of a rare, but serious and potentially fatal adverse effect with the use of
benzocaine sprays for medical procedures [Safety announcement, April 7,
2011]. Available at http://www.fda.gov/Drugs/DrugSafety/ucm250040.
htm.
Hurford WE, Kratz A. Case 23-2004. A 50-year-old woman with low
oxygen saturation. N Engl J Med 2004;351(4):380–387.
Chung NY, Batra R, Itzkevitch M, Boruchov D, Baldauf M. Severe methemoglobinemia linked to gel-type topical benzocaine use: a case report.
J Emerg Med 2010;38(5):601–606.
Janssen WJ, Dhaliwal G, Collard HR, Saint S. Clinical problem-solving.
Why “why” matters. N Engl J Med 2004;351(23):2429–2434.
El-Husseini A, Azarov N. Is threshold for treatment of methemoglobinemia the same for all? A case report and literature review. Am J Emerg Med
2010;28(6):748.e5–748.e10.

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