September 1, 2013 Volume 77, Number 9
ACE Question

You are preparing to provide an awake intubation and general anesthesia to a 64-year-old smoker with a history of extremely difficult tracheal intubation. Shortly after achieving topicalization of the airway with 20% benzocaine spray, the patient starts complaining of dyspnea and lightheadedness. His oxygen saturation measured by pulse oximetry declines to 84 percent and remains at that level despite the administration of 100 percent oxygen by facemask. Administration of which of the following would be the MOST appropriate therapy?

(A) Methylene blue

(B) Sodium thiosulfate

(C) Hydroxycobalamin

(D) Sodium nitrite

Benzocaine, available in 10 percent, 15 percent, and 20 percent solutions, is an ethyl ester of para-aminobenzoic acid; it is water soluble and widely used for topicalization of the airway during awake intubation. The 20 percent benzocaine solution contains 200 mg/mL, which can deliver between 60 mg (0.3 mL) to more than 200 mg (>1 mL) with every 1 second spray. Benzocaine is a component in Cetacaine, which contains 14 percent benzocaine, 2 percent tetracaine, and 2 percent butyl aminobenzoate. Benzocaine topicalization is associated with the development of methemoglobinemia. It has been recommended that the maximum dose of benzocaine for airway topicalization be limited to less than 1.5 mg/kg. Doses as small as 100 mg in adult patients can cause methemoglobinemia, especially in susceptible individuals.

There are many case reports in the literature of benzocaine-induced methemoglobinemia immediately following use of the spray, and this prompted the Food and Drug Administration (FDA) to issue a warning in 2003 as well as an advisory in 2006. In 2006 the U.S. Department of Veterans Affairs stopped the use of benzocaine within its hospital system.

Methemoglobin absorbs equal amounts of red and near-infrared light. The ratio of pulsatile and nonpulsatile absorbencies in the two wavelengths is equal to one at a hemoglobin oxygen saturation of 85 percent. Therefore, with high levels of methemoglobin a standard pulse oximeter will typically default to read a saturation of 85 percent regardless of the “true” oxygen saturation. Standard pulse oximetry is, therefore, unreliable as a monitor of actual oxygen saturation in patients with methemoglobinemia. One of the primary methods of diagnosis is a reduction in SpO2 values that is not consistent with the clinical situation in patients who have received agents associated with the development of methemoglobinemia.

The treatment of methemoglobinemia is intravenous methylene blue.

Sodium thiosulfate enhances the conversion of cyanide to thiocyanate. It is used to treat cyanide toxicity, not methemoglobinemia.

Amyl and sodium nitrite induce methemoglobin production in red cells and would therefore increase the level of methemoglobin. These drugs are used in the treatment of cyanide toxicity because methemoglobin combines with cyanide, displacing it from the cytochrome oxidase enzyme.

Hydroxycobalamin combines with cyanide to form cyanocobalamin (vitamin B12) and is then cleared by the kidneys. It has been approved by the FDA for treatment of known or suspected cyanide poisoning, not methemoglobinemia.

Answer: A

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• Sanchez A, Iyer RR, Morrison DE. Preparation of the patient for awake intubation. In: Hagberg CA, ed. Benumof’s Airway Management. 2nd ed. Philadelphia, PA: Elsevier Mosby; 2007:266.

• Morris IR. Preparation for awake intubation. In: Hung OR, Murphy MF, eds. Management of the Difficult and Failed Airway. New York, NY: McGraw-Hill; 2008:47.

• Nguyen ST, Cabrales RE, Bashour CA, et al. Benzocaine-induced methemoglobinemia. Anesth Analg. 2000;90(2):369–371.

• Public health advisory: benzocaine sprays marketed under different names, including Hurricaine, Topex, and Cetacaine. U.S. Food and Drug Administration website. Updated January 19, 2010. Accessed July 11, 2013.