Methylene blue or tolonium chloride antagonism of sodium nitrite induced methemoglobinemia

Methylene blue is widely accepted as an antidote for nitrite toxicosis because of its ability to stimulate reduction of methemoglobin (ferrihemoglobin) to hemoglobin. It is usually used only in low dosage (4mg/kg) because of its purported enhancement of methemoglobin formation in high dosages. Methylene blue was evaluated as a nitrite toxicosis antidote using methemoglobin reduction and lethality protection as evaluation parameters. Tolonium chloride (toluidine blue) another structurally related dye was also evaluated using the same parameters. Both dyes were very effective antidotes. Methylene blue increased in effectiveness as the dose was increased up to 22 mg/kg. Tolonium chloride provided approximately equivalent protection at 8.8 mg/kg but may be more toxic than methylene blue. High concentrations of either dye did not result in appreciable production of methemoglobin. In cases of severe intoxication by methemoglobin formers such as nitrite, larger doses of methylene blue than generally recommended, may be of considerable therapeutic value.