Methemoglobine

Methemoglobine, or methemoglobin, is an oxidized form of hemoglobin in which the iron in the heme group is ferric (Fe3+) and cannot bind oxygen. In healthy individuals, methemoglobin constitutes about 1–2% of total hemoglobin; it is continuously formed and normally reduced back to functional hemoglobin by enzymatic pathways, mainly NADH-dependent cytochrome b5 reductase.

Methemoglobine accumulation leads to methemoglobinemia. It can be acquired or inherited. Acquired forms result from exposure to oxidizing agents such as nitrates and nitrites (including contaminated water), benzocaine, prilocaine, aniline dyes, dapsone, sulfonamides, and other drugs. Congenital forms arise from deficiencies of methemoglobin-reducing enzymes, notably cytochrome b5 reductase, or from hemoglobin M variants.

Pathophysiology involves the inability of ferric iron to bind oxygen. Methemoglobin also increases the affinity of remaining normal hemoglobin for oxygen, reducing tissue oxygen delivery despite normal or near-normal PaO2. The clinical effect is hypoxia out of proportion to oxygen tension. The blood often appears chocolate-brown and may not turn red on exposure to air.

Clinical features include cyanosis that may be resistant to oxygen therapy, headache, dizziness, fatigue, tachycardia, and dyspnea. In infants, symptoms can be more severe due to lower reductase activity. Methemoglobinemia is diagnosed by co-oximetry showing elevated methemoglobin levels; pulse oximetry may plateau near 85% and there can be a saturation gap with arterial blood gas.

Treatment centers on removing the offending agent and, for significant cases, administering methylene blue (1–2 mg/kg IV, may be repeated; total daily dose typically limited). Methylene blue is contraindicated in G6PD deficiency and may fail in this context; alternative therapies include high-dose ascorbic acid or, in severe or refractory cases, exchange transfusion.