The congenital form of methemoglobinemia is most common in Alaskan Native Americans and individuals of Inuit descent . MHg levels in individuals with this congenital form of methemoglobinemia are usually between 15% and 30% of total hemoglobin, and individuals are normally asymptomatic except for varying degrees of persistent cyanosis. Another form of congenital methemoglobinemia occurs in individuals who display an aberrant form of hemoglobin (HbM), where the reduced ferrous ion is destabilized and is more easily oxidized to a ferric ion. In addition, the enzyme methemoglobin reductase cannot interact with and efficiently reduce the MHg in individuals displaying this form of hemoglobin.
Acquired methemoglobinemia occurs when an exogenous substance, typically a pharmacological agent, oxidizes hemoglobin producing MHg at rates 100 to 1000 times greater than it can be metabolized. Methemoglobinemia has been observed with a wide variety of different compounds including lidocaine, procaine, antimalarials, dapsone, nitrate derivatives such as nitroglycerin, nitrofuran, nitric oxide and nitroprusside, and numerous other compounds. Of particular importance to the endoscopist is the occurrence of methemoglobinemia with benzocaine-containing topical anesthetics. The incidence of benzocaine-induced methemoglobinemia in bronchoscopy is estimated to be one in 7000 exposures and is most common in pediatric and elderly patients.