Methemoglobinemia

A unique systemic side effect associated with a specific local anesthetic is the development of methemoglobinemia after the administration of large doses of prilocaine.^[180] A dose-response relationship exists between the amount of prilocaine administered epidurally and the degree of methemoglobinemia; in general, 600-mg doses are required for the development of clinically significant levels of methemoglobin in adults. The metabolism of prilocaine in the liver results in the formation of O-toluidine, which is responsible for the oxidation of hemoglobin to methemoglobin.^[181] The methemoglobinemia associated with the use of prilocaine is spontaneously reversible or may be treated by the intravenous administration of methylene blue. With increased use of EMLA (which contains prilocaine) in neonates and young infants, there has been concern regarding the risk of methemoglobinemia.^[182] Standard dosing of EMLA in term newborns produced minimal amounts of methemoglobin, and EMLA should be regarded as very safe in the great majority of newborns. Risk may be increased in rare newborns made more susceptible by metabolic disorders and concomitant administration of other drugs that impair the reduction of methemoglobin. ^[182]