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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Reported adverse event cases of methemoglobinemia associated with benzocaine products.

BACKGROUND: Methemoglobinemia (MHb) is characterized by abnormal levels of oxidized hemoglobin that cannot bind and transport oxygen. When induced by benzocaine anesthetic spray and other chemicals, it can result in cyanosis and life-threatening complications. METHODS: From 818 439 adverse event reports received by the US Food and Drug Administration from November 1997 through March 2002, we extracted every report for use of a benzocaine product. We classified each case by product type (eg, spray, gel, or solution), by whether MHb was involved, and by the dose given. RESULTS: Among 198 reported adverse events of all types associated with benzocaine, 132 cases (66.7%) involved definite or probable MHb. The MHb cases included 107 serious adverse events (81.1%) and 2 deaths (1.5%). In 123 cases (93.2%), the product was a spray; in 2 cases (1.5%), a benzocaine-containing lozenge; and 1 case, a gel. In the 69 cases that specified a dose, 37 (53.6%) indicated that a single spray was applied (approximately the recommended amount). CONCLUSIONS: Health professionals involved in endoscopy, intubation, bronchoscopy, or similar invasive procedures using benzocaine-containing sprays should know that (1) administration may cause MHb with potentially serious consequences, (2) identifying the reaction to benzocaine usually requires cooximetry (although it can be implied by symptoms), and (3) treatment involves immediate intravenous administration of 1 to 2 mg/kg of methylene blue.[1]


  1. Reported adverse event cases of methemoglobinemia associated with benzocaine products. Moore, T.J., Walsh, C.S., Cohen, M.R. Arch. Intern. Med. (2004) [Pubmed]
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